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Guidelines for managing community-acquired pneumonia in need of re-evaluation
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“Pneumonitis” denotes inflammation of pulmonary parenchymal tissue, either alveolar or interstitial, resulting from any one of several known pathophysiologic mechanisms. However, in more generic terms, the clinical term “pneumonia” — often described by radiographers as “air space disease” — is conceptualized by most as an infectious disease. Health care providers are led to this diagnostic determination when evaluating patients who present with clinical features such as cough, pleuritic chest pain, dyspnea, fever, hypoxemia, mucopurulent sputum production, leukocytosis, pulmonary auscultatory findings, and the demonstration of a new or changing infiltrative lung process on radiologic chest imaging.
The current classification of pneumonia separates this entity into three categories: community-acquired, hospital-acquired and ventilator-associated pneumonia (CAP, HAP and VAP). This triad classification scheme follows a recent recommendation by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) to remove “health care-associated pneumonia” as a distinct entity. Patients with CAP should be covered for multidrug-resistant (MDR) organisms based on validated risk factors (eg, nursing home residence, antibiotic use in past 90 days, prior known infections with same), but not those with HAP. Other than assessing one’s chances of having the etiologic agent(s) causing their infection be an MDR organism, the designation of CAP, HAP, and VAP plays an important and influential role in decision-making, such as site of treatment, diagnostic testing and aspects of antimicrobial and adjunctive therapies. Moreover, features distinct to each classification of pneumonia are central to epidemiologic investigations; formulation of guidelines and policies; assessment of quality measures by hospitals, health care systems and regulatory agencies; and the design and implementation of interventions employed in infection prevention. That being said, perhaps the most important aspects of classifying and managing pneumonia are elucidated by statistical analyses of the morbidity, mortality and overall health care expenditures associated with the infectious disease.
In the United States, approximately 5 to 6 million cases of CAP are diagnosed annually. About 20% to 25% of patients are hospitalized, 10% of whom are directly admitted to or eventually managed in the ICU. Each year, the estimated costs associated with hospitalized CAP patient care exceed $10 billion. Although pneumonia and influenza are the eighth leading cause of mortality among adults — resulting in an estimated 60,000 deaths annually — CAP alone has been identified as the principal cause of infectious disease-related mortality and the leading cause of sepsis. The in-hospital and 30-day all-cause mortality rates associated with CAP are substantial — 10% and 23%, respectively. Furthermore, irrespective of age, CAP also confers a high risk for long-term morbidity and mortality compared with the general population, with death occurring in 30.6% of patients within 1 year of hospitalization, according to one report.
In 2007, IDSA and ATS published their first combined consensus guidelines on the management of CAP in adults, replacing previously issued independent guidelines. Interestingly, as stated in their executive summary, the guidelines were intended primarily for use by emergency medicine physicians, hospitalists and primary care practitioners. This suggests a knowledge gap between infectious disease and pulmonary specialists and physicians on the “front lines” when it comes to the evaluation and management of respiratory ailments, which are notably the most prevalent reasons people seek medical attention and the most common indications given for the prescribing of outpatient antibiotics, whether they are appropriate or not.
As with all practice guidelines, the anticipated purpose is purported “to update clinicians with regard to important advances and controversies in the management” of a particular disease state, in this instance CAP, with the intention of improving outcomes (most significantly mortality rates) and reducing expenditures. The IDSA/ATS joint committee clearly recognized that the guidelines may not specifically apply to each individual patient or clinical scenario, are strictly voluntary and are meant to be applied at the discretion of the treating physician. Nonetheless, besides being quoted on rounds or at conferences by medical residents as if they were the 11th commandment, the guidelines are routinely referred to as the “standard of care” at hospital peer-review and quality committees, as well as in medicolegal matters. Furthermore, governmental and accrediting organizations (ie, CMS and The Joint Commission) employ these guidelines when creating “core measures,” which have potential financial consequences for those who are out of compliance.
In the 11 years that have elapsed since the publication of the CAP guidelines, there has been much debate and discussion over many of the recommendations, both informally and in the medical literature, even between some of the joint committee members. The updated IDSA/ATS CAP guidelines currently are in progress.
The following are some considerations.
Site-of-care decisions
The decision of whether or not a patient with suspected or proven CAP needs hospitalization may be summed up best by the words of Bob Dylan: “You don’t need a weatherman to know which way the wind blows.” In the current everyday clinical practice of medicine, the choice between inpatient vs. outpatient management of pneumonia goes well beyond hemodynamic, respiratory and laboratory parameters and the need for parenteral medication. A multitude of social and economic considerations (support at home, insurance coverage, time of day presenting to the ED, etc.), as well as the clinical acumen, competence, sense of security and perception of the medical care provider, heavily impact this determination. Treating CAP in the hospital exponentially escalates costs and increases patient complications (eg, health care-associated conditions), which are used as benchmarks to financially punish or reward both hospital systems and physicians.
Therefore, in an attempt to standardize the admission decision process and avoid unnecessary admissions, the current guideline strongly recommends the use of two severity-of-illness and mortality prognosis objective scoring systems — the Pneumonia Severity Index, or PSI (see Box 1) and CURB-65 (see Box 2). Nationally, less than one-quarter of patients reported to have CAP are ever hospitalized, but up to 50% or more of patients who present to the ED for presumed CAP are admitted to the hospital. This perhaps suggests a different standard of care for some ED providers, or perhaps it is because the patients are “already there.” Moreover, nearly one-fifth of patients are admitted directly to the ICU, the major criteria for which should be the need for hemodynamic vasopressor support or mechanical ventilation. However, per the guideline’s moderate recommendation, the choice between admission to the ICU or the general unit warrants consideration in patients who exhibit at least three of nine minor criteria for severe CAP that, along with other scoring algorithms, have been found to predict the chance of clinical deterioration and the eventual need for invasive ventilation or vasopressor therapy. However, other than the obvious immediate or heightened concern of the need for cardiopulmonary stability support, no data exist showing that subsequent deterioration would be better prevented by direct admission to the ICU rather than to a regular unit. Logically, all other appropriate diagnostic and treatment interventions should be equally available in either hospital unit location (except for more rapid attention in the ICU). Furthermore, there are studies demonstrating that strict adherence to “scores” results in a significant number of unwarranted ICU admissions. In one recent publication (albeit in a pediatric population), more than half of children classified as having severe CAP according to Pediatric Infectious Diseases Society/IDSA criteria were not even admitted to the hospital and did not receive interventions or have diagnoses that necessitated hospitalization.
Diagnostic testing
Modern-day medicine’s access to a multitude of medications, medical devices and surgical and nonsurgical invasive procedures has tangibly transformed practice from what was once essentially a diagnostic profession to one that is now focused on treatment. Nonetheless, the answer to the question, “What are you treating?” still deserves considerable attention. In practical terms, though, other than influencing a specific treatment, serving as an indicator of prognosis, or having an effect on future medical or public health issues, the potential benefits of diagnostic testing need to be weighed against the use of personnel and other resources. Realistically speaking, aside from point-of-care influenza virus testing, microbiological diagnostic tests in outpatients with CAP rarely are done and do not seem to have a measurable effect on outcomes. On the other hand, those who are hospitalized routinely have a host of studies performed — once again, because they are “already there” — although the tangible benefit of having this costly additional information is up for debate.
The lack of sensitivity of blood cultures (~10% positive in hospitalized patients with CAP, almost all being Streptococcus pneumoniae) suggests they should be limited to critically ill patients with CAP admitted to the ICU especially because, in nonsevere infections, the detection of bacteremia often represents a false-positive finding or contaminant, which may lead to unjustified treatment.
Gram’s stain and culture of sputum suffer from limited sensitivity and less specificity than blood cultures. The urine Legionella antigen assay is sensitive but only detects L. pneumophilia group 1 (~80% of community-onset Legionnaires’ disease cases). More sophisticated testing (eg, selective sputum cultures) would be helpful in those with negative urine antigen results but who have syndromes suggesting Legionella pneumonia. An S. pneumoniae (pneumococcal) urine antigen test has been available since 1999. According to one large published survey, it is used regularly by 65% of ID physicians but less than 20% of the time if non-ID physicians are managing the patient alone. One impediment to its use is the unavailability of the test in many community hospital laboratories, requiring physicians to use a reference laboratory, which delays turnaround times. Although the test has at least 90% specificity in patients with pneumococcal pneumonia, its lackluster 50% to 80% sensitivity is greatly influenced by the presence of concurrent bacteremia (present in a minority of cases). It also has a poor negative predictive power. Moreover, unless the antibiotic management is under the control of an ID specialist, de-escalation or the narrowing of antibiotic therapy is unlikely to happen because many physicians justify continuing an empiric treatment because “it’s working, so why change it?” In fact, in one study, the results of the urine antigen test led to a reduction in the spectrum of antibiotics in only 9% of CAP patients.
Since the 2007 CAP guideline publication, several very sensitive and specific multiplex respiratory pathogen PCR panels designed to detect the most common respiratory viruses and Mycoplasma pneumoniae and Chlamydia pneumoniae have become clinically available. However, technical requirements for test performance restrict their use to hospitalized CAP patients. In addition, all of the viruses included in the assays (other than influenza) may be present in the upper respiratory tract solely as colonizers. Although its reported detection rates have been as high as 86% in studies governed by strict selection criteria, it is unrealistic to think that similar success could be achieved in routine clinical practice. Molecular PCR diagnostic assays, cultures and serologic and antigen detection tests were used in the prospective CDC Etiology of Pneumonia in the Community (EPIC) study, which was conducted in hospitalized adult patients. Notwithstanding the use of these more sensitive and specific tests, a specific etiologic agent was identified in only 38% of patients. Viruses were detected in 62% of patients with positive results, bacteria in 29% and both bacteria and viruses in 7% — the top four being human rhinovirus, influenza virus, S. pneumoniae and human metapneumovirus. Of the 853 patients who had any pathogen isolated, from a pool of 2,259 with diagnostic results, only 75 had Mycoplasma or Legionella, either alone or as a co-pathogen.
More recently, the serum biomarker procalcitonin has been advocated for use in CAP patients as an indirect diagnostic marker of bacterial infection (for more information on procalcitonin, see page 55). The hope is that this information will help to curtail unnecessary antibiotic prescriptions and assist in the decision to limit the duration of antibiotic therapy, assuming it was indicated to start with. However, one large multicenter trial failed to show a reduction in antibiotic use between patients with suspected lower respiratory tract infections who were assigned to procalcitonin-guided treatment vs. patients who received usual care.
It is hoped that, over time, the use of the respiratory panels along with procalcitonin levels will result in less use of antibiotics when all indications are viral illnesses.
Antibiotic treatment
Antibiotics prescribed for the treatment of presumed CAP are usually selected empirically. The reason is that 80% of CAP is treated on an outpatient basis with little or no attempt to make an etiologic diagnosis. In hospitalized patients, despite all efforts, no pathogen is identified in almost two-thirds of cases. The role of antibiotics is to inhibit or preferably kill the bacteria and thus decrease the inflammatory immune response. Therefore, the antibiotic agent chosen needs to have dependable antimicrobial activity (based on known resistance data as well as pharmacodynamic principals), not only against the most likely bacterial pathogen(s), but against those that are most prone to lead to severe illness and sepsis. When treating CAP, the major organism of concern clearly is S. pneumoniae. Consequently, knowing the degree of pneumococcal resistance to macrolides and minimal drug serum concentration of certain agents (ie, azithromycin), the current IDSA/ATS recommendation of a macrolide agent alone for outpatients appears to be inappropriate and stands in contrast to European (eg, United Kingdom and Sweden) CAP guidelines. Furthermore, if the patient is determined to have a more severe case of CAP requiring admission to the hospital, the recommendation of combining a beta-lactam agent (eg, ceftriaxone) with the macrolide or choosing a respiratory fluoroquinolone medication alone would imply a greater concern for pneumococcal disease and a lack of confidence in a macrolide being an adequate antibiotic choice. Because S. pneumoniae is the most probable respiratory bacterial pathogen to cause severe infection, it begs the question, “Why risk treating with a macrolide alone in any case of CAP?”
Additionally, as demonstrated in the EPIC study, atypical bacterial pathogens appear to be significantly less prevalent in hospitalized patients with CAP than the recommendations would suggest. The Community-Acquired Pneumonia – Study on the Initial Treatment with Antibiotics of Lower Respiratory Tract Infections (CAP-START) concluded that among patients in non-ICU wards, treatment with beta-lactam monotherapy was noninferior to a beta-lactam-macrolide combination or fluoroquinolone monotherapy with regard to 90-day all-cause mortality, length of stay or the incidence of complications. Conceivably, we need a more thorough discussion on which clinical features signify a greater chance of an atypical respiratory bacterial infection.
Despite the guidelines, clinicians still tend to add vancomycin or linezolid to their empiric antibiotic CAP treatment regimen (29.8% of the time in one community multicenter study, even though less than 1% were found to have a MRSA infection). In this realm, stronger recommendation statements are needed. One such recommendation should be rapid and inexpensive routine MRSA nasal screening of patients admitted to the hospital with CAP. Although a positive test is not diagnostic of MRSA pneumonia, a negative test essentially excludes the diagnosis, with a proven negative predictive value of 95%.
Based on the initial route of fluoroquinolone administration, a large retrospective cohort study comparing outcomes in hospitalized patients with CAP who were treated intravenously vs. orally failed to identify any significant differences in outcomes. This information, as well as our agreement that “the bug does not know how the drug got there,” it is hoped will provide the impetus to recommend oral therapy more often in the forthcoming practice guideline. Lastly, as has been demonstrated in treating other infectious diseases, shorter courses of antibiotics for CAP result in equivalent outcomes, and this deserves a stronger recommendation in future guidelines.
Corticosteroids and pneumonia
At face value, the use of corticosteroids, with their known immunosuppressive effects, would appear to be counterintuitive as part of the management of CAP. However, their beneficial role in the treatment of other infectious diseases such as community bacterial and tuberculous meningitis, typhoid fever as well as CAP in patients with COPD, among others, lends support to their consideration in the treatment of CAP. A meta-analysis of randomized trials of corticosteroids for CAP demonstrated a decreased risk for adult respiratory distress syndrome and reductions in antibiotic use and length of stay, without an increase in major adverse events. Validation of their becoming a more accepted part of CAP management also calls for more guideline input.
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- For more information:
- Larry M. Bush, MD, FACP, is an affiliated professor of biomedical sciences at the Charles E. Schmidt College of Medicine, Florida Atlantic University, and affiliated associate professor of medicine at the University of Miami Miller School of Medicine, JFK Medical Center, Palm Beach County, Florida.
- Donald Kaye, MD, MACP, is a professor of medicine at Drexel University College of Medicine, associate editor of the International Society for Infectious Diseases’ ProMED-mail, section editor of news for Clinical Infectious Diseases and an Infectious Disease News Editorial Board member.
Disclosures: Bush and Kaye report no relevant financial disclosures.