Healthcare-Associated Pneumonia

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CME/CE Information

Introduction

Healthcare-associated pneumonia (HCAP), a newly recognized form of pneumonia, was included in the 2005 American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) guidelines for nosocomial pneumonia.^[1] HCAP refers to patients with pneumonia, at any time in their hospital stay (on admission or acquired in the hospital), who have a history of recent hospitalization in the past 90 days, residence in a nursing home or extended care facility, treatment with chronic hemodialysis, receipt of home wound care, or exposure to a family member with drug-resistant pathogen infection. There remains confusion about how to best define this entity, what the likely pathogens are, and how to optimally approach therapy and prevention. In addition, the guidelines considered that patients with HCAP are at risk for infection with multidrug-resistant (MDR) gram negatives and methicillin-resistant Staphylococcus aureus (MRSA). Thus, the current recommendation is to treat HCAP patients with multidrug broad-spectrum empirical therapy, a practice that may promote further antibiotic resistance, particularly if such broad-spectrum therapy is not needed for all affected individuals. At the 2007 ATS meeting, a symposium was held to discuss HCAP and the controversies in management and prevention. Topics discussed included defining HCAP epidemiology and bacteriology, the approach to diagnosis, therapy and prevention, and evaluation of the best way to use effective therapy while minimizing the promotion of antimicrobial resistance, leading to optimal patient outcomes.

Epidemiology and Bacteriology

Like community-acquired pneumonia (CAP), HCAP can be present when the patient is first admitted to the hospital, but unlike CAP, and similar to nosocomial pneumonia, the etiologic pathogens can be MDR gram negatives and MRSA. A study by Kollef and colleagues^[2] noted that this difference in bacteriology is likely a consequence of the fact that HCAP patients have more comorbid illness than patients with CAP. These comorbidities include immunosuppression, diabetes, chronic renal disease, heart disease, and stroke. Marcos Il Restropo, MD, from the University of Texas, San Antonio, discussed unpublished data from his own institution where all HCAP patients had MDR risk factors, which included prior antibiotics, residence in a nursing home, chronic renal failure, and immunosuppression. One other unpublished study from Washington University in St. Louis, Missouri, found that HCAP was more common than CAP, and that 63% of these patients had been recently hospitalized; 31% were immunosuppressed; 18% were nursing home residents; and 6% were undergoing hemodialysis.
Dr. Restropo described studies documenting the bacteriology of HCAP to include a high frequency of MRSA and Pseudomonas aeruginosa.^[2] In one study, the frequency of MRSA was 57% but 25% had P aeruginosa,^[2] whereas in another study of patients with MDR gram negatives present on admission, there was a high frequency of HCAP risk factors, including recent antibiotics and residence in a long-term care facility.^[3] When patients with MRSA were compared with those with methicillin-susceptible S aureus (MSSA) infection in another study using a case-control methodology, once again, prior hospitalization, home nursing care, and transfer from a nursing home were all associated with the presence of MRSA.^[4]
The higher frequency of these difficult pathogens in patients with HCAP may explain why their mortality rate of 12% to 23% is higher than that of patients with CAP. To minimize this mortality risk, Dr. Restropo urged the use of early and aggressive appropriate empirical therapy, with a broad-spectrum antimicrobial approach followed by de-escalation to fewer drugs and narrower spectrum agents, as culture and clinical data become available. In addition, he recommended use of therapy at proper doses, as suggested in the ATS/IDSA guidelines, and he recommended linezolid over vancomycin for the therapy of MRSA ventilator-acquired pneumonia (VAP).^[1] One additional suggestion that he discussed was to use short-duration therapy, citing a French study that documented the efficacy of 8-day therapy of VAP caused by organisms other than nonfermenting gram negatives, such as P aeruginosa.^[5]

Pathogenesis and Prevention of HCAP

David Ost, MD, from New York University School of Medicine, New York, NY, discussed the pathogenesis and use of risk factors to guide the prevention of VAP, in an effort to understand how to avoid other nosocomial pneumonia syndromes, including HCAP. He cited the impact of VAP on hospital stay, which increases stay by 7-9 days, while adding a cost of nearly $12,000 per episode.^[6]
Dr. Ost pointed out the imprecision of clinical definitions of VAP, showing that depending on the number of criteria used, the frequency of infection can vary from 8% to 30%, but that by any definition, VAP leads to adverse outcomes. In addition, the frequency, when expressed as a daily risk rate, falls with increasing duration of mechanical ventilation, emphasizing the need for prevention studies to stratify patients by the duration of mechanical ventilation. Given this important impact of VAP, prevention could have a high reward, and efforts should be based on an understanding of both modifiable and unmodifiable risk factors -- and might reduce the incidence by as much as 50%.^[7] On the basis of an understanding of modifiable risks, the effective strategies for prevention that Dr. Ost recommended included rapid weaning from the ventilator, including daily interruption of sedation; use of noninvasive ventilation when possible; positioning patients with the head of the bed elevated; using open lung ventilation if possible; avoidance of nasotracheal intubation in favor of orotracheal intubation; treatment in an adequately staffed intensive care unit (ICU); careful consideration of selective digestive decontamination (with topical and systemic antibiotics, but not topical alone) to reduce the risk for gram-negative infection; consideration of chlorhexidine baths; and consideration of sucralfate for intestinal bleeding prophylaxis. Dr. Ost emphasized the difference between efficacy in clinical trials and true clinical effectiveness in "real-world" situations. He stated that the use of subglottic secretion drainage with special endotracheal tubes and specific enteral feeding methods could not be specifically recommended.

Diagnosing Nosocomial Pneumonia

Kenneth V. Leeper, MD, from the Emory School of Medicine in Atlanta, Georgia, discussed the controversies surrounding invasive vs noninvasive diagnosis of VAP. His major focus was to examine which approach could minimize the impact of VAP on mortality, length of stay, antibiotic use, antibiotic resistance, and duration of mechanical ventilation. He first discussed the recently published, Canadian, multicenter clinical trial comparing invasive and noninvasive diagnostic methods, and demonstrating no impact on mortality.^[8] He criticized the trial because it did not enroll many patients with MDR pathogens.
In trying to define the most cost-effective approach to VAP diagnosis, Dr. Leeper first examined noninvasive strategies. He pointed out that the clinical definition of pneumonia has a relatively low sensitivity and specificity in some studies, but that if too sensitive a definition were used, it could lead to the overuse of antibiotics and a failure to recognize nonpneumonic causes of fever. He pointed out the potential value of the Clinical Pulmonary Infection Score (CPIS) to enhance the noninvasive diagnosis of VAP, and cited a study by Singh and colleagues^[9] in which antibiotic cost, antibiotic resistance, and mortality were reduced when a protocol employing serial measurements of CPIS was used to guide antibiotic therapy, when compared with usual clinical management. He also showed how clinical management could be used to guide duration of therapy, and lead to less systemic antibiotic use.
Looking at the putative advantages of an invasive diagnostic approach, Dr. Leeper cited the potential to avoid unnecessary and inappropriate antibiotic therapy, and to be able to narrow and focus antibiotics once culture data from quantitative cultures of lower respiratory tract secretions become available. He discussed a review^[10] that reported the sensitivity of bronchoscopic diagnosis to be between 42% and 93%, with a specificity varying between 45% and 100%. Early studies documented the safety of withholding therapy in patients with negative quantitative cultures and a low clinical suspicion of infection, but a large French multicenter study comparing an invasive bronchoscopic approach with a noninvasive strategy for antibiotic use showed a reduction in 14-day mortality and antibiotic use.^[11] One alternative to bronchoscopic cultures is blind minibronchoalveolar lavage (BAL) done through an endotracheal tube, and one decision analysis showed that the best approach to maximize VAP survival, while minimizing cost and antibiotic use, was to give empirical therapy with 3 antibiotics and then adjust on the basis of mini-BAL culture data.^[12] Dr. Leeper advocated this approach, but stated that at his institution the decision to start therapy was also guided by CPIS, but the decision to continue or modify therapy was, in part, based on the results of a repeat mini-BAL, done after 4 days of therapy.

Managing HCAP and Reducing the Risk for Antimicrobial Resistance

There are various ways to limit antibiotic resistance by managing risk factors in the patient with HCAP. Not only have the resistance rates in nosocomial pneumonia been rising in recent years, especially if infection is caused by P aeruginosa or MRSA, but in one recent German study, infection with these pathogens was an independent risk factor for mortality, using multiple logistic regression analysis.^[13] A number of factors have led to rising rates of resistance, including inappropriate use of antibiotics, underdosing of key antimicrobial agents, using a broader spectrum of therapy than is needed, unnecessary treatment of airway colonization, excessively prolonged therapy, and failure of infection control methods. Common to many of these factors is the usage of antibiotics, and many investigations have shown that usage within 2 weeks of the onset of VAP is a risk for subsequent resistance to the previously used antibiotic.^[14,15]
In a discussion, which I led at this meeting, I highlighted a number of potentially effective strategies to limit resistance, which included infection control, surveillance respiratory cultures, avoiding monotherapy with certain antimicrobial agents, avoiding broader antimicrobial therapy than is necessary, antimicrobial "stewardship," de-escalation of therapy when possible, and more effective "up-front" therapy. Infection control is a universal need, and it can limit the spread of resistant pathogens from one patient to another. In addition, infection control practitioners can facilitate a good knowledge of local (specific for each ICU) microbiology. A study by the Duke University Infection Control Network, collecting such data and sharing best practices, led to a reduction in the frequency of VAP and of infections caused by MRSA.^[16]
A number of strategies have led to the use of fewer and more focused antibiotics, and because usage is the major factor driving resistance, these strategies could be very valuable. These have included the collection of tracheal aspirate surveillance cultures, which can be used to guide initial VAP empirical therapy, and in one study this practice led to the use of less broad-spectrum therapy than the use of international guidelines.^[17] Careful selection of specific antimicrobials is also an effective strategy to limit resistance, because monotherapy with third-generation cephalosporins can promote the emergence of extended-spectrum beta-lactamases and the emergence of inducible type 1 chromosomal beta-lactamases during therapy.^[1,18] In addition, quinolones can promote antimicrobial resistance, not only to quinolones, but also to multiple other agents, and, thus, I suggested that in the ICU, these agents should generally be reserved for a second episode of infection -- and not the first acquired infection -- because the latter practice may make it impossible to have any effective agents for subsequent infection.^[15]
In an effort to avoid the use of broader spectrum therapy than is absolutely necessary, we examined the recommendation of current guidelines to treat all HCAP patients with a 3-drug regimen geared at resistant gram negatives and MRSA.^[1] Citing a study, from Buffalo, New York, of 88 patients with severe nursing home-acquired pneumonia, he pointed out that resistant organisms were only present in 19%, and that they were present only if patients had multiple risk factors, in addition to severe illness.^[19] Because narrow-spectrum therapies have been effective for some nursing home populations, he recommended that triple therapy be reserved for patients with at least 2 of the 3 key risk factors, and that patients without these risks be treated with a narrower spectrum regimen. These risk factors were severe illness, recent antibiotic therapy, and poor functional status.
A recent IDSA publication examined the practices of antimicrobial stewardship, emphasizing the multidisciplinary nature of this effort, which can be done through prospective audits and interventions or by formulary restrictions.^[20] The recommendation for formulary restrictions was not strong, but the study authors did recommend use of therapy guidelines that are based on local bacteriologic data, de-escalation of therapy when possible, and dose optimization. Antimicrobial cycling and antibiotic order forms were not strongly recommended.
In closing, I recommended a number of other strategies to limit resistance, including shorter durations of therapy. One way to facilitate this approach may be to follow serial measurements of biological markers, such as C-reactive protein and procalcitonin. One other promising strategy that was discussed is the use of adjunctive aerosolized aminoglycosides to optimize the initial therapy of MDR gram negatives. I described unpublished data from a multicenter study of aerosolized amikacin, given by a special proprietary nebulizer, in a blinded placebo-controlled fashion, along with systemic antimicrobials (all patients received this latter therapy). The data showed that at the end of 7 days, patients given aerosol antibiotic therapy were using less systemic antibiotics than patients given a placebo aerosol, raising the possibility that this approach can eradicate infection rapidly and minimize the need for prolonged systemic therapy.

Using Pathophysiology and Risk Factors to Optimize HCAP Outcomes

Richard G. Wunderink, MD, FCCP, from Feinberg School of Medicine, Northwestern University, Chicago, Illinois, focused on ways to improve the outcomes, especially mortality, duration of ICU stay, duration of mechanical ventilation, and the degree of organ dysfunction in patients with HCAP. He referred to a study of MRSA VAP in which the use of linezolid, rather than vancomycin, led to a reduction in mortality.^[21]
The major focus of the discussion was to evaluate antimicrobial treatment failure and recurrent infection as signs of immunosuppression in the critically ill patient, especially as a consequence of immune paralysis at the time of severe infection. Dr. Wunderink considered 2 possible types of explanations for this immune dysfunction, both with supporting data: temporary disease-related immune impairment and fixed immune impairment as a consequence of genetic polymorphisms in the immune response. He advocated the use of biomarkers to follow the course of the immune response to infection. He believed that the major focus for the future would be to understand this immune paralysis and recognize it when present, so that interventions could be made to improve outcomes. Currently, because we do not have such interventions, we are limited to changing antibiotics in the face of uncontrolled infection, finding unrecognized sites of infection, and replacing immunoglobulins in patients who are deficient.
Supported by an independent educational grant from GlaxoSmithKline

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References

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References

1. Niederman MS, Craven DE, Bonten MJ, et al. 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. Abstract
2. Kollef MH, Shorr A, Tabak YP, et al. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture positive patients. Chest. 2005;128:3854-3862. Abstract
3. Pop-Vicas AE, D'Agata EM. The rising influx of multidrug-resistant gram-negative bacilli into a tertiary care hospital. Clin Infect Dis. 2005;40:1792-1798. Abstract
4. Lescure FX, Locher G, Eveillard M, et al. Community-acquired infection with healthcare-associated methicillin-resistant Staphylococcus aureus: the role of home nursing care. Infect Control Hosp Epidemiol. 2006;27:1213-1218. Abstract
5. Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003;290:2588-2598. Abstract
6. Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med. 2002;165:867-903. Abstract
7. Bonten MJ, Kollef MH, Hall JB. Risk factors for ventilator-associated pneumonia: from epidemiology to patient management. Clin Infect Dis. 2004;38:1141-1149. Abstract
8. The Canadian Critical Care Trials Group. A randomized trial of diagnostic techniques for ventilator-associated pneumonia. N Engl J Med. 2006;355:2619-2630. Abstract
9. Singh N, Rogers P, Atwood CW, et al. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med. 2000;162:505-511. Abstract
10. Torres A, El-Ebiary M. Bronchoscopic BAL in the diagnosis of ventilator-associated pneumonia. Chest. 2000;117:198S-202S. Abstract
11. Fagon JY, Chastre J, Wolff M, et al. Invasive and noninvasive strategies for management of suspected ventilator-associated pneumonia: a randomized trial. Ann Intern Med. 2000;132:621-630. Abstract
12. Ost DE, Hall CS, Joseph G, et al. Decision analysis of antibiotic and diagnostic strategies in ventilator-associated pneumonia. Am J Respir Crit Care Med. 2003;168:1060-1067. Abstract
13. Gastmeier P, Sohr D, Geffers C, et al. Risk factors for death due to nosocomial infection in intensive care unit patients: findings from the Krankenhaus Infektions Surveillance System. Infect Control Hosp Epidemiol. 2007;28:466-472. Abstract
14. Trouillet JL, Vuagnat A, Combes A, et al. Pseudomonas aeruginosa ventilator-associated pneumonia: comparison of episodes due to piperacillin-resistant versus piperacillin-susceptible organisms. Clin Infect Dis. 2002;34:1047-1054. Abstract
15. Niederman MS. Reexamining quinolone use in the intensive care unit: use them right or lose the fight against resistant bacteria. Crit Care Med. 2005;33:443-444. Abstract
16. Kaye KS, Engemann JJ, Fulmer FM, et al. Favorable impact of an infection control network on nosocomial infection rates in community hospitals. Infect Control Hosp Epidemiol. 2006;27:228-232. Abstract
17. Michel F, Franceschini B, Berger P, et al. Early antibiotic treatment for BAL-confirmed ventilator-associated pneumonia: a role for routine endotracheal aspirate cultures. Chest. 2005;127:589-597. Abstract
18. Paterson DL, Ko WC, Von Gooberg A, et al. International prospective study of Klebsiella pneumoniae bacteremia: implications of extended-spectrum beta-lactamase production in nosocomial infections. Ann Intern Med. 2004;140:26-32. Abstract
19. El Solh AA, Pietrantoni C, Bhat A, et al. Indicators of potentially drug-resistant bacteria in severe nursing home-acquired pneumonia. Clin Infect Dis. 2004;39:474-480. Abstract
20. Dellit TH, Owens RC, McGowan JE, et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007;44:159-177. Abstract
21. Wunderink RG, Rello J, Cammarata SK, et al. Linezolid vs vancomycin: analysis of two double-blind studies of patients with methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Chest. 2003;124:1789-1797. Abstract