Current Perspectives on Pneumonia in Clinical Practice

Introduction to Perspectives on Pneumonia

The increased concerns of drug resistance in managing lung disease affects both hospitalized and outpatient populations. In this expert interview with Michael Niederman, MD, of State University of New York and Winthrop University Hospital conducted by Medscape editor Jennifer Brown, PhD, the risks for pneumonia in special populations are considered. The current management trends to prevent and treat pneumonia caused by ever-evolving pathogens are put into a clinical perspective in the following commentary.

Patients at Risk for Pneumonia

Medscape: Welcome, Dr. Niederman, and thank you for sharing your perspectives on pneumonia. What patient populations are currently considered to be at increased risk for bacterial, viral, or fungal pneumonia?

Dr. Niederman: All 3 forms of pneumonia can affect virtually any individual, but in general the paradigm for any type of pneumonia is the balance between the patient's host defenses, the virulence of the potential pathogen, and the size of the exposure to the pathogen. So in theory, pneumonia can develop even in healthy individuals if they encounter particularly virulent pathogens or very large inoculum. So for example, an individual who gets severe acute respiratory syndrome (SARS) encounters a virus so virulent that it is impossible to have host defenses against it. On the other hand you can have a large inoculum of bacteria, which could overwhelm a healthy defense system. A good example is a young, otherwise healthy individual who gets drunk, vomits, and aspirates such a large quantity of bacteria that pneumonia develops. The majority of the patients we see in the hospital who have pneumonia tend to be individuals with impaired host defenses, either as a result of advanced age, underlying comorbid medical conditions, or medications. Because of their impaired immune systems not only are these individuals more prone to infection, but when pneumonia develops, it is a more severe infection.

Comorbid conditions could be congestive heart failure, chronic obstructive pulmonary disease (COPD), cigarette smoking, or underlying malignancy. A variety of medications that we routinely use increase the risk for infection. Even something as simple as aspirin has been shown to interfere with immune defenses and can predispose some patient populations to pneumonia. Certainly advanced age is also an important factor. There is some controversy about whether it is the age itself or the diseases that develop as a result of getting older. It is probably to some extent the combination of both.

Medscape: Are there special concerns for the immunocompromised, for example, those who take medications that are immunosuppressive?

Dr. Niederman: There are concerns, and the most common immunosuppressive drugs of concern used in clinical practice are probably corticosteroids. Individuals who are chronically treated with corticosteroids, as might be the case in those with COPD, rheumatoid arthritis, or other inflammatory diseases, are more prone to bacterial and viral infections as a result of their steroid therapy. Chemotherapy immune-related suppression can develop in individuals receiving chemotherapy, which particularly predisposes them to bacterial and fungal infections. With the biologic therapies that interfere with cell-mediated immunity, particularly the anti-tumor necrosis factor types of therapies, there has been a much greater concern about tuberculosis than pneumonia. Anything that interferes with immune defenses can predispose a patient to both bacterial and fungal infections.

Medscape: In patients with, for example HIV or a disease that has made them immunocompromised, what are the particular risks for pneumonia?

Dr. Niederman: There is a risk for immunocompromised patients. The way to evaluate that risk is to look at the abnormality the patient has to know, for example, what that does to the immune system. Then you can better predict what types of pathogens are likely to cause infection. So for example, people who are infected with HIV can have predominantly abnormalities of cell-mediated immunity but they can also have antibody formation abnormalities. Therefore, they are on the one hand predisposed to things like tuberculosis and atypical microbacteria and unusual fungal infections. In addition, they're also greatly at risk for pneumococcal pneumonia.

If you look for example at patients who have neutropenia because of cancer and chemotherapy, they are particularly predisposed to Gram-negative bacteria. So if you can define the nature of the immunosuppression and where specifically it affects the immune system, this can help you better predict which specific types of pathogens are likely to be problematic.

Evaluating Causes of Pneumonia

Medscape: In patients with cystic fibrosis in particular, what are the most common causes of pneumonia you see?

Dr. Niederman: The 2 pathogens that have been a problem in cystic fibrosis are Staphylococcus aureus, which tends to be a pathogen earlier in the disease and Pseudomonas aeruginosa, which tends to be a pathogen later in the disease. But there are a variety of unusual Gram-negative bacteria that have been a problem with cystic fibrosis as the disease gets more advanced. Here the factors that predispose patients to infection tend to be the cystic fibrosis itself, which leads to alterations in production of mucous, quality of the mucous, and clearance of the mucous. All of these can predispose to specific bacteria. Inevitably because of their disease, patients with cystic fibrosis are frequently treated with antibiotics. The treatment can then predispose to emergence of particularly resistant forms of Gram negative bacteria that tend to be problematic later in the disease.

Medscape: How would you determine the cause in a patient who has symptoms of pneumonia, whether bacterial, viral, or fungal?

Dr. Niederman: I think one of the issues that people are struggling with right now is this question, is it possible to look at a patient and know whether their infection is bacterial or viral? Efforts in the past included can you tell by the clinical syndrome, can you tell by the radiographic patterns, by the fever, by the white cell count? Many studies have been done but they have not yet shown that clinical features can separate bacterial from viral infections. One of the reasons this is important is if you can predict who has a viral infection with some accuracy, then you could say that this person doesn't need antibacterial therapy. Since we are concerned about the overuse of antibiotics and how that could be driving resistance, it would be helpful in theory to be able to predict who has which.

A particularly promising approach right now involves serum measurements of procalcitonin.^[1] When procalcitonin measurements are low, they exclude bacterial disease, as low procalcitonin levels seem to occur in viral infection. Studies in patients who have x-ray-positive pneumonia and low procalcitonin levels who have been randomized to observation without antibiotics have done very well without antibiotic therapy. This is one potential measurement for the future.

Today, for most patients, we look at their clinical features. If there is any chance that it is bacterial, we treat them with antibiotics and we try to identify the bacterial pathogen. Sputum samples are used if patients are intubated and the tracheal aspirates or bronchoscopic samples are cultured. We examine them microscopically to identify suspicious bacterial infections, and to identify what bacteria.

Medscape: Are agent-specific tests recommended for regular use?

Dr. Niederman: Generally agent-specific tests are not routinely used. Agent-specific tests widely available right now include urinary antigen testing for Legionella and Pneumococcus species. The problem with specific-agent tests in community-acquired pneumonia (CAP) is that it's difficult to know when the test is positive and how it should affect your approach to treatment. There are some new-onset cases and complexities of treatment. For example, there is a dataset of patients who have been in infected with Pneumococcus, who have pneumococcal bacteremia, who seem to benefit by the addition of a second antibiotic. If that is reproducible, then it would be hard to imagine how doing a specific test for Pneumococcus that was positive might change the antibiotic therapy. It might narrow it if you have a broad-spectrum therapy because of the possibility of needing a second antibiotic. But Legionella and Pneumococcus urinary antigen tests are probably the most specific tests in use.

The other common approach is to culture sputum, tracheal aspirates, bronchoscopic samples, or lower respiratory tract samples in patients who have suspected or confirmed pneumonia.

Current Practice for Treating Pneumonia

Medscape: What are the current medications of choice and how is the therapy selection individualized for the patient newly diagnosed with pneumonia?

Dr. Niederman: Guidelines for treating patients with CAP, with healthcare-associated pneumonia (HAP), and with nosocomial pneumonia depend on the severity of illness, the comorbidities of the patients, and the time of onset of the illness in the case of nosocomial infection. There are a variety of different algorithms for therapy, but no single best therapy. The 2005 guidelines for nosocomial pneumonia were a joint effort of American Thoracic Society and the Infectious Disease Society of America, as were the 2007 guidelines for CAP.^[2,3]

In general, with CAP, we treat for pneumococcus and generally the possibility of atypical pathogen co-infection. Some subpopulations are treated for Gram-negative bacteria. For patients who have HAP, coming from a nursing home or the hospital in the previous 3 months, they are at much greater risk for drug-resistant Gram negative infections and methicillin-resistant S aureus, and these patients need therapies directed to those pathogens. In nosocomial pneumonia it depends on how late in the course of the hospital stay pneumonia developed. Have they recently been on antibiotics? What are the pathogens that are common in a given hospital? All of these factors then get considered in terms of choosing an antibiotic therapy.

Strategies for Preventing Pneumonia

Medscape: Considering care of the elderly, could you please comment on strategies to prevent pneumonia in this population?

Dr. Niederman: I think in the elderly, 3 factors may play a role in their increased risk for infection. One is aging itself, and there is some controversy whether that really plays a role. The medications that the elderly get, and also the comorbidities that they have both play a role. For the elderly, many medications and comorbidities are associated with the risk for pneumonia. In terms of prevention, prevention of pneumonia generally involves smoking cessation and vaccination for patients outside of the hospital setting. For the elderly individual who is residing outside of the hospital, whether it's in the nursing home or at home, vaccination, including both pneumococcal and influenza vaccines, are probably the 2 most important preventive strategies that we have right now. In the hospital a whole series of preventive measures is undertaken.

Medscape: A recent report indicated vaccinating even the young had a positive effect for preventing pneumonia in others with HIV in the population.

Dr. Niederman: This is an interesting observation, the concept of herd immunity. When the 7-valent conjugant vaccine for Pneumococcus ^[4] (PCV7) was widely used in children, it had a benefit in elderly individuals, particularly the ones caring for the children. It seemed that if you eliminated the reservoir of Pneumococcus in young children, you might then eliminate the distribution source, if you will, of the Pneumococcus to older individuals who came in contact with the children. Very compelling data showed that with the early use of the vaccine in children there was a decline in the frequency of those strains of Pneumococcus in elderly individuals. This paralleled the decline in children, and the speculation was that they were therefore not transmitting the Pneumococcus at the same rate to the elderly caregivers around them.

Another twist to that data on vaccinating the young should be watched very closely. There have now been reports that with continued use of PCV7, there appears to be a decline in the frequency of the strains covered in that vaccine. They have been replaced at a higher frequency by other strains that aren't covered. In particular there are some very severe, necrotizing strains of Pneumococcus that aren't covered by the current vaccine that have emerged at higher frequency in vaccinated individuals. The concern is that the Pneumococcus being able to adapt to this vaccination strategy has now replaced some of the vaccine strains with other strains, some of which are more virulent, and that effect may be that there is more severe pneumonia occurring in certain populations than was appearing before the vaccine was introduced.^[5] So if that turns out to be true and can be confirmed in other populations, it may negate some of that herd immunity benefit that has been seen in the nonvaccinated individuals.

Medscape: What preventive measures would you say are helpful in the hospital setting to reduce HAP?

Dr. Niederman: Well the big issue right now in the hospital is the focus on mechanically ventilated patients, and there a lot of efforts have revolved around something that has been referred to as a "ventilator bundle." It's a bundling of interventions that many hospitals do in an effort to reduce the frequency of pneumonia. The typical bundle most widely promoted and used involves 5 elements, two of which are part of the bundle but really are good patient care that can help reduce intensive care unit stay and may indirectly reduce pneumonia but don't directly interfere with pneumonia pathogenesis. Those are gastrointestinal bleeding prophylaxis and deep venous thrombosis prophylaxis.

The other 3 interventions in the bundle are much more pneumonia-specific. One is elevation of the head of the bed with the idea of minimizing gastric reflux into the oropharynx and then aspiration into the lung. Keeping the head of the bed elevated can reduce gastric transmission of bacteria to the lungs. The 2 others are a daily interruption of sedation -- you wake the patient up every day, and when you do that there is a daily effort of weaning. That is the fifth element. So the bundle is: daily interruption of sedation and daily weaning trials, head of the bed elevation, deep vein thrombosis and gastrointestinal bleeding prophylaxis.

Although these bundles are probably effective, their advent has led to some interesting discussions and controversies. Some individuals are reporting that with the use of ventilator bundles they have eliminated pneumonia from their hospital. Some hospitals have even said we have gone as long as 2 years without an episode of ventilator associated pneumonia because of how valuable these bundles are and how successful we've been in implementing them.

The problem with those reports has been that many studies report a lower frequency of pneumonia in ventilated patients, but don't seem to report secondary benefits, meaning overall reduction in use of antibiotics, reduction in mortality, reduction in length of stay -- the known consequences of VAP. The diagnosis of VAP can often be subjective, and it's an elusive, difficult diagnosis. The worry is that people are now saying they don't have pneumonia in their hospital, but it isn't as credible as you would like because the secondary consequences of pneumonia are not also disappearing.

All of this has become increasingly more controversial because Medicare has proposed, and it's unclear what the final decision will be, that VAP should be considered a potential medical error that should not be given additional reimbursement. If so, the concern is that many hospitals would report very low rates of pneumonia. However, it's not clear to me that they're really eliminating the problem. It seems like there are populations of patients who are at such high risk because of their underlying comorbidities, chronic illness, and acute illness that they can't possibly have a zero-risk for pneumonia, even in the best hands and in the best hospitals.

Medscape: That really leads us directly into the Hospital Compare Web site. What impact will public reporting have on practice, or how will it change how patients choose hospitals?

Dr. Niederman: The Hospital Compare Web site right now is looking at CAP, but it may become part of the Medicare database that they'll be publicly reporting on VAP rates, and I would make the distinction. I think that in general it is good that pneumonia has become a target of public reporting, that people are aware of the importance of pneumonia. It is the number one cause of death from infectious diseases in the United States, and we are doing everything we can to reduce the frequency of pneumonia.

But you have to wonder whether the public reporting can have some unintended consequences that are not positive. One worry in the VAP side is if we have public reporting of very low VAP rates, that sort of strains credibility. There are populations where it's impossible to get the rates as low as some people report; you wonder if they are simply redefining the illness and haven't really made progress. What I worry about personally is that if we say pneumonia is a medical error, VAP, and it really is not eliminated, it will really, I think, hamper future research in this area. It would be very difficult for people to want to investigate a disease that when it occurs, it is considered bad medical care. So I think we have to get very accurate and honest in defining how low we can reduce these rates.

The Hospital Compare Web site, which compares different hospitals and their compliance with CAP, in general has been helpful. The one area that I think it still controversial is the antibiotic timing measure that Medicare has instituted. Originally that was looking at the frequency with which antibiotics were given within 4 hours and that has now been changed to 6 hours. But the concern has been that if it becomes publicly reported that 4 hours is the standard, then hospitals will inevitably try to get that rate to 100%. I think that many experts believe that 100% compliance with the 4-hour rule isn't necessarily good medical care. There may be cases of medical uncertainty, and so as another modification they have introduced medical uncertainty as an exemption to this 4-hour rule.

Published reports have raised concern about the 4-hour antibiotic timing rule. There are now 2 retrospective studies that show that when hospitals try to comply with the 4-hour rule, in general they give antibiotics to more patients, but the frequency with which the antibiotics were used for a final discharge of CAP actually dropped. In other words, many more patients got antibiotics but some of them got antibiotics when they didn't really have pneumonia.

Another consequence is at least one report of a hospital with very bad episodes of infection with Clostridium difficile. The majority of the episodes occurred in patients who were treated with antibiotics for pneumonia, but half of those patients who were treated for pneumonia didn't, in retrospect, have pneumonia. This occurred at a time period when the hospital was trying to be more compliant with the antibiotic timing measure.

I think that the Hospital Compare Web site is generally a good idea, but the goals that are set in comparison have to be accurate and realistic. What I worry about is that when the data get published publicly, everyone is going to look for the hospital that has the highest number. You have to recognize that it might be possible for some of these measures, that the highest number may not necessarily equal the desired goal. The desired goal might be 85% rather than 100% for some of these measures. It might be that there is a bell-shaped curve where the best care occurs when the compliance rate for a hospital is 80% to 85%. People below that and above that might not be providing the best possible care.

Source : http://www.medscape.com/viewarticle/577190