P n eum on i a Challenges in the Definition, Diagnosis, and Management of Disease Julie Ottosen,
MD,
Heather Evans,
MD, MS*
KEYWORDS Hospital-acquired pneumonia (HAP) Ventilator-associated pneumonia (VAP) Pulmonary Aspiration Infection KEY POINTS Definitions of the different subtypes of pneumonia are imprecise. Although communityacquired pneumonia is its own entity, ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) fall under the umbrella of health care–associated pneumonia. Aspiration pneumonia is a distinct process, which may begin in the communal setting, but is often and sometimes inappropriately labeled a health care–associated event. Early HAP may be related to events occurring before hospitalization that are not subject to quality improvement. Because VAP is associated with poor outcomes (including longer duration of mechanical ventilation, cost of care, morbidity, and mortality), preventative measures should be used. Quantitative lower respiratory tract cultures should be collected from all patients before antibiotic therapy. However, this procedure should not delay initiation of therapy in critically ill patients. Early broad-spectrum antibiotics with appropriate dosing should be used. De-escalation of antibiotic therapy should be considered once data from lower respiratory tract cultures are available. Negative lower respiratory tract cultures can be used to stop antibiotic therapy in those who have had cultures obtained in the absence of antibiotic therapy within 72 hours. A shorter duration of antibiotic therapy for uncomplicated HAP (7–8 days) should be used in patients who show an appropriate clinical response. Patients with trauma may be at increased risk for VAP because of chest trauma, head injury, depressed levels of consciousness, need for surgery mandating multiple intubations, and aspiration complicating urgent intubation. In patients with lower Injury Severity Scores (ISS), VAP is an independent risk factor for death. More severely injured patients with trauma (ISS >25) seem to succumb to their injuries, and the contributory role of VAP is less clear.
No financial support was received for this publication. Division of Trauma, Critical Care, and Burns, Harborview Medical Center, 325 Ninth Avenue, Box 359796, Seattle, WA 98104, USA * Corresponding author. E-mail address: [email protected] Surg Clin N Am 94 (2014) 1305–1317 http://dx.doi.org/10.1016/j.suc.2014.09.001 surgical.theclinics.com 0039-6109/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
1306
Ottosen & Evans
DEFINING PNEUMONIA
Despite thousands of studies devoted to the topic of hospital-acquired pneumonia (HAP), controversies in the definition and management of HAP still remain. Perhaps the most important distinction to be made is what differentiates communityacquired pneumonia (CAP) from HAP, because the treatment paradigms and quality improvement issues vary between the 2. HAP, or nosocomial pneumonia, arises 48 hours or more after hospital admission in the absence of signs or symptoms of pneumonia at the time of admission. VAP is a subtype of HAP that develops after endotracheal intubation. Because only about 10% of patients with HAP are not mechanically ventilated, the terms HAP and VAP are often used interchangeably. However, the causative organisms of VAP have been isolated from the oropharynx and stomach, and this must be considered when deciding on empirical therapy.1 Pneumonia that occurs early in the course of hospital stay is addressed as early onset pneumonia. However, it is difficult to define the cutoff that distinguishes early from late, because it is unknown how long it takes to develop pneumonia after the aspiration of microorganisms. Most studies have used a cutoff of 4 days, or 96 hours. Regardless, when the concept of early versus late is used, it is essential to designate hospital admission, not intubation, as day 1. This designation is based on the premise that the bacterial milieu of the oropharynx is influenced over time by the health care environment and interventions, giving the disease more the bacterial characteristics and antibiotic sensitivities of late onset pneumonia.2 Late onset pneumonia occurs later in the course of hospital stay (>96 hours) and is associated with poorer outcomes. It is considered a preventable disease and therefore a target for quality improvement. However, it may be difficult to avoid in severely ill patients who are immunocompromised, with poor physiologic reserve and inability to clear secretions. In such situations, it may be considered a terminal event. In 2005, the American Thoracic Society (ATS) guidelines defined a new category of infections to encompass recent inpatient or on ongoing treatment in a long-term or outpatient health care facility. The health care–associated pneumonia (HCAP) definition includes any patient who was hospitalized in an acute care hospital for 2 or more days within 90 days of the infection; resided in a nursing home or long-term care facility; received recent intravenous antibiotic therapy, chemotherapy, or wound care within the past 30 days of the current infection; or attended a hospital or hemodialysis clinic.3 Such infections may be caused by community microorganisms, but are designated particularly to alert providers as to the increased risk of multidrug-resistant strains that may be transmitted in health care facilities. Definitions of HAP, HCAP, and VAP were not designed with quality assessment in mind. They are nonspecific and do not correlate with histopathologic findings of pneumonia, irrespective of the method of microbiological sampling.4,5 Recently, the Centers for Disease Control and Prevention have implemented an alternative surveillance paradigm for patients who are mechanically ventilated. Recognizing the subjectivity and poor reproducibility of clinical definitions, the working group designed the new surveillance definitions to be more objective, more efficient to collect via electronic medical record data, and more standardized across institutions.6 However, in practice, these definitions may have little correlation with the clinical practice of the diagnosis of VAP, with poor sensitivity and substantial variation in incidence rates, with subtle changes in electronic implementation (Table 1).7 To add to the challenge, early onset VAP may be related to aspiration events occurring before intubation and admission to the intensive care unit (ICU) and not
Definition, Diagnosis, and Management of Pneumonia
Table 1 Syndromes and definitions Syndrome
Definition
VAP
New or progressive and persistent infiltrate on chest radiograph plus 2 of the following: abnormal white blood cell count (12,000), presence of fever or hypothermia (38 C), purulent sputum, and deterioration in gas exchange
VAC
An increase in daily minimum positive end-expiratory pressure >3 or an increase of the daily minimum FiO2 >.20 sustained for 2 calendar days in a patient who had a baseline period of stability or improvement on the ventilator, defined by 2 calendar days of stable or decreasing daily minimum FiO2 or positive end-expiratory pressure
iVAC
An episode of VAC associated with alteration in white blood cell count (>12,000 or 38 C or 4 d of new antibiotics
Abbreviation: iVAC, infection related ventilator associated condition; VAC, Ventilator associated condition.
necessarily attributable to poor quality of care, and it is unclear as to the impact of early aspiration on the risk of late pneumonia. Lung and general host defenses play a significant role in the development of HAP, and for a given inoculum, the risk of developing pneumonia is highly influenced by these. This finding also confounds the analysis of quality of care. INCIDENCE
VAP is one of the most common hospital-acquired infections, occurring in 10% to 20% of ICU admissions in large database analyses from the late 1990s.8,9 In 2010, the US Centers for Disease Control and Prevention reported more than 3500 cases. The reported incidence in patients with trauma is generally higher, up to twice that of the general ICU population.10 Depressed levels of consciousness secondary to head injury and sedation, need for emergent surgery and anesthesia, and emergent intubation all place this population at particularly high risk for the development of infectious pulmonary disease.11 Patients with trauma are also at increased risk because of underlying chest trauma and lung injury.12 DEFINING SEVERITY OF PNEUMONIA
The severity of pneumonia is, necessarily, contextual. Possible microbial cause, benefit from specific therapies, benefit from experimental therapies, and estimations of morbidity and mortality may be contingent on initial assessment of disease severity. There is considerable interest in the use of novel and potentially disease-specific biomarkers to distinguish pneumonia from other systemic illness, and to classify pneumonia severity. Of these novel biomarkers, most attention has focused on procalcitonin, a prohormone to calcitonin involved in chemoattraction and nitric oxide production. A variety of pulmonary specific biomarkers such as RAGE, HMGB-1, sTREM, and pro-ANP require further study. A variety of nonspecific biomarkers are already used routinely, including serum bilirubin, lactate, and platelet count. For the evaluation of CAP, simple measures of multiple organ dysfunction may be more useful than any of the newer assays, as suggested by the 2007 Infectious Diseases Society of America (IDSA) guidelines, which incorporate platelet count and renal function into the initial patient assessment of illness severity.13
1307
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Ottosen & Evans
DEFINITIONS GUIDING ANTIBIOTIC USE
Delay in treatment with antibiotics is associated with poorer outcomes in sepsis and HAP in particular. Initial treatment with broad-spectrum antibiotics, to be narrowed at a future date, is recommended. Use of antifungals is not routine but should be considered for very high risk populations (ie, immunocompromised patients). CAUSATIVE ORGANISMS
Bacterial, fungal, or viral agents may be responsible for the onset of CAP. In healthy adults, Haemophilus influenza and Streptococcus pneumoniae are the most common agents. Mycoplasma pneumonia, Chlamydia pneumoniae, and Legionella pneumonia are rarer but plausible atypical agents. Viruses such as influenza and respiratory syncytial virus should be considered. In immunocompromised patients, fungal infections such as Pneumocystis jirovecii (previously carinii) must also be suspected. Likely causative organisms for VAP depend on whether the infection is early or late onset. Early (within the first 96 hours) is more likely to be antibiotic sensitive, whereas VAP developing 96 hours after intubation is associated with more antibiotic-resistant organisms. This finding varies by unit and season, which emphasizes the importance of maintaining current unit-specific antibiograms. Regardless, the later form is associated with a higher morbidity and mortality. PREDICTIVE MODELS
Critical for early decision making in the treatment of CAP is determination of the level of care required, ranging from outpatient oral antibiotic therapy to intubation and ICU admission. The Pneumonia Severity Index (PSI) is one of many tools devised for the assessment of the severity of CAP at presentation in the emergency department.14 With the PSI model, patient risk scores are determined by 4 risk categories: demographic factors, comorbid conditions, findings on physical examination, and degree of physiologic derangement as indicated by laboratory results. Points in each category are stratified to 1 of 5 risk classes. For the patient with the lowest risk, outpatient treatment is recommended. For those found to be at high risk (class 4 1), inpatient treatment is recommended. Similar to the PSI, the PIRO (predisposition, insult, response, and organ dysfunction) score incorporates variables classified according to the patient’s predisposition, insult, response, and organ dysfunction on presentation with CAP and has been shown to be more predictive of outcome in ICU patients than APACHE II score or ATS/IDSA criteria.15 Although perhaps not as accurate as the PSI or PIRO, the CURB-65 model (named after confusion, urea, respiratory rate, blood pressure) is a simpler decision support tool for use in determining the level of care required based on the severity of presenting symptoms of CAP.16,17 A score of 1 or 2 indicates a patient who may be treated in the outpatient setting, whereas a score of 31 suggests inpatient therapy (Table 2). Table 2 CURB65 score. One point is assigned for each matched criteria C
Confusion
U
Blood urine nitrogen >20
R
Respiratory rate >30 breaths/min
B
Systolic blood pressure 36.5 and 38.5 and 240 or acute respiratory distress syndrome
Chest radiograph
No infiltrate
Tracheal aspirate culture
Negative
6 at baseline is suggestive of pneumonia.
Definition, Diagnosis, and Management of Pneumonia
tract secretions for quantitative cultures. In patients with acute respiratory distress syndrome, deterioration of radiographic images because of progression of pulmonary infection may be difficult to detect, and suspicion for pneumonia should be high to avoid delays in treatment. Similarly, patients with chest trauma may have difficult in interpreting radiographs, and a low threshold for microbiological sampling is appropriate. Blood cultures should be obtained, because VAP with bacteremia is associated with increased mortality compared with VAP alone.29 However, there are no clear data to support that information from blood cultures either significantly alters treatment or improves outcomes. Ideally, blood and quantitative airway cultures should be obtained before initiating or manipulating antibiotics. This strategy may not be possible in all situations. For instance, a patient may already be on antimicrobial therapy for another source of infection. When this is the case, decreasing the bacterial colony count threshold for defining pneumonia may be of benefit. Delay in the initiation of appropriate antibiotic therapy may increase disease morbidity and mortality, especially in patients with septic shock requiring ongoing vasoactive agent support. Therefore, under these circumstances, initiation of antimicrobials should not be postponed for the purpose of performing diagnostic workup. Clinical signs of infection in patients with negative lower respiratory tract cultures should prompt investigation for extrapulmonary sites of infection. By nature, patients managed in an ICU are at risk for several forms of hospital-acquired infection and should be evaluated thoughtfully and broadly. EMPIRICAL THERAPY
Immediate administration of appropriate antibiotic therapy is essential in the treatment of pneumonia. However, antimicrobial treatment is not without risk. In particular, for a patient receiving prolonged broad-spectrum antibiotics, antibiotic pretreatment shows a considerable microbial selection pressure associated with excess mortality. The key decision in initial empirical therapy is determining whether the patient has risk factors for multidrug-resistant (MDR) strains. The distinction between early and late onset pneumonia has classically been used to tailor drug therapy. However, patients admitted after recent hospitalization or from long-term care facilities may also be at increased risk for MDR pathogens. The overall approach to treatment is shown in the algorithm in Fig. 1. INITIAL ANTIBIOTIC SELECTION AND DOSING
Optimal dosing remains a matter of debate. Differences in pharmacokinetics, microbiological characteristics of underlying pathogens, and methodology applied to determine microbial resistance levels all influence the antimicrobial effect of a given dosage. Moreover, penetration into lung tissue is an important factor that should be considered when selecting an antimicrobial regimen. Aminoglycosides are not ideal, because they achieve a lung penetration rate of only 30% to 40%. b-Lactams also have a penetration of less than 50%. Fluoroquinolones, in contrast, show cellular and lung tissue penetration 100% of serum level. Several studies have reported better clinical outcomes using linezolid compared with vancomycin for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, supported by the superior lung penetration of the drug.30
1311
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Ottosen & Evans
Fig. 1. Approach to empirical therapy for HAP and VAP.
Differences between spontaneously breathing versus ventilated patients are not firmly settled, and drug-resistant organisms may affect both populations. Therefore, recommendations in these 2 settings are frequently similar. For early onset pneumonia (
MD,
Heather Evans,
MD, MS*
KEYWORDS Hospital-acquired pneumonia (HAP) Ventilator-associated pneumonia (VAP) Pulmonary Aspiration Infection KEY POINTS Definitions of the different subtypes of pneumonia are imprecise. Although communityacquired pneumonia is its own entity, ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) fall under the umbrella of health care–associated pneumonia. Aspiration pneumonia is a distinct process, which may begin in the communal setting, but is often and sometimes inappropriately labeled a health care–associated event. Early HAP may be related to events occurring before hospitalization that are not subject to quality improvement. Because VAP is associated with poor outcomes (including longer duration of mechanical ventilation, cost of care, morbidity, and mortality), preventative measures should be used. Quantitative lower respiratory tract cultures should be collected from all patients before antibiotic therapy. However, this procedure should not delay initiation of therapy in critically ill patients. Early broad-spectrum antibiotics with appropriate dosing should be used. De-escalation of antibiotic therapy should be considered once data from lower respiratory tract cultures are available. Negative lower respiratory tract cultures can be used to stop antibiotic therapy in those who have had cultures obtained in the absence of antibiotic therapy within 72 hours. A shorter duration of antibiotic therapy for uncomplicated HAP (7–8 days) should be used in patients who show an appropriate clinical response. Patients with trauma may be at increased risk for VAP because of chest trauma, head injury, depressed levels of consciousness, need for surgery mandating multiple intubations, and aspiration complicating urgent intubation. In patients with lower Injury Severity Scores (ISS), VAP is an independent risk factor for death. More severely injured patients with trauma (ISS >25) seem to succumb to their injuries, and the contributory role of VAP is less clear.
No financial support was received for this publication. Division of Trauma, Critical Care, and Burns, Harborview Medical Center, 325 Ninth Avenue, Box 359796, Seattle, WA 98104, USA * Corresponding author. E-mail address: [email protected] Surg Clin N Am 94 (2014) 1305–1317 http://dx.doi.org/10.1016/j.suc.2014.09.001 surgical.theclinics.com 0039-6109/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
1306
Ottosen & Evans
DEFINING PNEUMONIA
Despite thousands of studies devoted to the topic of hospital-acquired pneumonia (HAP), controversies in the definition and management of HAP still remain. Perhaps the most important distinction to be made is what differentiates communityacquired pneumonia (CAP) from HAP, because the treatment paradigms and quality improvement issues vary between the 2. HAP, or nosocomial pneumonia, arises 48 hours or more after hospital admission in the absence of signs or symptoms of pneumonia at the time of admission. VAP is a subtype of HAP that develops after endotracheal intubation. Because only about 10% of patients with HAP are not mechanically ventilated, the terms HAP and VAP are often used interchangeably. However, the causative organisms of VAP have been isolated from the oropharynx and stomach, and this must be considered when deciding on empirical therapy.1 Pneumonia that occurs early in the course of hospital stay is addressed as early onset pneumonia. However, it is difficult to define the cutoff that distinguishes early from late, because it is unknown how long it takes to develop pneumonia after the aspiration of microorganisms. Most studies have used a cutoff of 4 days, or 96 hours. Regardless, when the concept of early versus late is used, it is essential to designate hospital admission, not intubation, as day 1. This designation is based on the premise that the bacterial milieu of the oropharynx is influenced over time by the health care environment and interventions, giving the disease more the bacterial characteristics and antibiotic sensitivities of late onset pneumonia.2 Late onset pneumonia occurs later in the course of hospital stay (>96 hours) and is associated with poorer outcomes. It is considered a preventable disease and therefore a target for quality improvement. However, it may be difficult to avoid in severely ill patients who are immunocompromised, with poor physiologic reserve and inability to clear secretions. In such situations, it may be considered a terminal event. In 2005, the American Thoracic Society (ATS) guidelines defined a new category of infections to encompass recent inpatient or on ongoing treatment in a long-term or outpatient health care facility. The health care–associated pneumonia (HCAP) definition includes any patient who was hospitalized in an acute care hospital for 2 or more days within 90 days of the infection; resided in a nursing home or long-term care facility; received recent intravenous antibiotic therapy, chemotherapy, or wound care within the past 30 days of the current infection; or attended a hospital or hemodialysis clinic.3 Such infections may be caused by community microorganisms, but are designated particularly to alert providers as to the increased risk of multidrug-resistant strains that may be transmitted in health care facilities. Definitions of HAP, HCAP, and VAP were not designed with quality assessment in mind. They are nonspecific and do not correlate with histopathologic findings of pneumonia, irrespective of the method of microbiological sampling.4,5 Recently, the Centers for Disease Control and Prevention have implemented an alternative surveillance paradigm for patients who are mechanically ventilated. Recognizing the subjectivity and poor reproducibility of clinical definitions, the working group designed the new surveillance definitions to be more objective, more efficient to collect via electronic medical record data, and more standardized across institutions.6 However, in practice, these definitions may have little correlation with the clinical practice of the diagnosis of VAP, with poor sensitivity and substantial variation in incidence rates, with subtle changes in electronic implementation (Table 1).7 To add to the challenge, early onset VAP may be related to aspiration events occurring before intubation and admission to the intensive care unit (ICU) and not
Definition, Diagnosis, and Management of Pneumonia
Table 1 Syndromes and definitions Syndrome
Definition
VAP
New or progressive and persistent infiltrate on chest radiograph plus 2 of the following: abnormal white blood cell count (12,000), presence of fever or hypothermia (38 C), purulent sputum, and deterioration in gas exchange
VAC
An increase in daily minimum positive end-expiratory pressure >3 or an increase of the daily minimum FiO2 >.20 sustained for 2 calendar days in a patient who had a baseline period of stability or improvement on the ventilator, defined by 2 calendar days of stable or decreasing daily minimum FiO2 or positive end-expiratory pressure
iVAC
An episode of VAC associated with alteration in white blood cell count (>12,000 or 38 C or 4 d of new antibiotics
Abbreviation: iVAC, infection related ventilator associated condition; VAC, Ventilator associated condition.
necessarily attributable to poor quality of care, and it is unclear as to the impact of early aspiration on the risk of late pneumonia. Lung and general host defenses play a significant role in the development of HAP, and for a given inoculum, the risk of developing pneumonia is highly influenced by these. This finding also confounds the analysis of quality of care. INCIDENCE
VAP is one of the most common hospital-acquired infections, occurring in 10% to 20% of ICU admissions in large database analyses from the late 1990s.8,9 In 2010, the US Centers for Disease Control and Prevention reported more than 3500 cases. The reported incidence in patients with trauma is generally higher, up to twice that of the general ICU population.10 Depressed levels of consciousness secondary to head injury and sedation, need for emergent surgery and anesthesia, and emergent intubation all place this population at particularly high risk for the development of infectious pulmonary disease.11 Patients with trauma are also at increased risk because of underlying chest trauma and lung injury.12 DEFINING SEVERITY OF PNEUMONIA
The severity of pneumonia is, necessarily, contextual. Possible microbial cause, benefit from specific therapies, benefit from experimental therapies, and estimations of morbidity and mortality may be contingent on initial assessment of disease severity. There is considerable interest in the use of novel and potentially disease-specific biomarkers to distinguish pneumonia from other systemic illness, and to classify pneumonia severity. Of these novel biomarkers, most attention has focused on procalcitonin, a prohormone to calcitonin involved in chemoattraction and nitric oxide production. A variety of pulmonary specific biomarkers such as RAGE, HMGB-1, sTREM, and pro-ANP require further study. A variety of nonspecific biomarkers are already used routinely, including serum bilirubin, lactate, and platelet count. For the evaluation of CAP, simple measures of multiple organ dysfunction may be more useful than any of the newer assays, as suggested by the 2007 Infectious Diseases Society of America (IDSA) guidelines, which incorporate platelet count and renal function into the initial patient assessment of illness severity.13
1307
1308
Ottosen & Evans
DEFINITIONS GUIDING ANTIBIOTIC USE
Delay in treatment with antibiotics is associated with poorer outcomes in sepsis and HAP in particular. Initial treatment with broad-spectrum antibiotics, to be narrowed at a future date, is recommended. Use of antifungals is not routine but should be considered for very high risk populations (ie, immunocompromised patients). CAUSATIVE ORGANISMS
Bacterial, fungal, or viral agents may be responsible for the onset of CAP. In healthy adults, Haemophilus influenza and Streptococcus pneumoniae are the most common agents. Mycoplasma pneumonia, Chlamydia pneumoniae, and Legionella pneumonia are rarer but plausible atypical agents. Viruses such as influenza and respiratory syncytial virus should be considered. In immunocompromised patients, fungal infections such as Pneumocystis jirovecii (previously carinii) must also be suspected. Likely causative organisms for VAP depend on whether the infection is early or late onset. Early (within the first 96 hours) is more likely to be antibiotic sensitive, whereas VAP developing 96 hours after intubation is associated with more antibiotic-resistant organisms. This finding varies by unit and season, which emphasizes the importance of maintaining current unit-specific antibiograms. Regardless, the later form is associated with a higher morbidity and mortality. PREDICTIVE MODELS
Critical for early decision making in the treatment of CAP is determination of the level of care required, ranging from outpatient oral antibiotic therapy to intubation and ICU admission. The Pneumonia Severity Index (PSI) is one of many tools devised for the assessment of the severity of CAP at presentation in the emergency department.14 With the PSI model, patient risk scores are determined by 4 risk categories: demographic factors, comorbid conditions, findings on physical examination, and degree of physiologic derangement as indicated by laboratory results. Points in each category are stratified to 1 of 5 risk classes. For the patient with the lowest risk, outpatient treatment is recommended. For those found to be at high risk (class 4 1), inpatient treatment is recommended. Similar to the PSI, the PIRO (predisposition, insult, response, and organ dysfunction) score incorporates variables classified according to the patient’s predisposition, insult, response, and organ dysfunction on presentation with CAP and has been shown to be more predictive of outcome in ICU patients than APACHE II score or ATS/IDSA criteria.15 Although perhaps not as accurate as the PSI or PIRO, the CURB-65 model (named after confusion, urea, respiratory rate, blood pressure) is a simpler decision support tool for use in determining the level of care required based on the severity of presenting symptoms of CAP.16,17 A score of 1 or 2 indicates a patient who may be treated in the outpatient setting, whereas a score of 31 suggests inpatient therapy (Table 2). Table 2 CURB65 score. One point is assigned for each matched criteria C
Confusion
U
Blood urine nitrogen >20
R
Respiratory rate >30 breaths/min
B
Systolic blood pressure 36.5 and 38.5 and 240 or acute respiratory distress syndrome
Chest radiograph
No infiltrate
Tracheal aspirate culture
Negative
6 at baseline is suggestive of pneumonia.
Definition, Diagnosis, and Management of Pneumonia
tract secretions for quantitative cultures. In patients with acute respiratory distress syndrome, deterioration of radiographic images because of progression of pulmonary infection may be difficult to detect, and suspicion for pneumonia should be high to avoid delays in treatment. Similarly, patients with chest trauma may have difficult in interpreting radiographs, and a low threshold for microbiological sampling is appropriate. Blood cultures should be obtained, because VAP with bacteremia is associated with increased mortality compared with VAP alone.29 However, there are no clear data to support that information from blood cultures either significantly alters treatment or improves outcomes. Ideally, blood and quantitative airway cultures should be obtained before initiating or manipulating antibiotics. This strategy may not be possible in all situations. For instance, a patient may already be on antimicrobial therapy for another source of infection. When this is the case, decreasing the bacterial colony count threshold for defining pneumonia may be of benefit. Delay in the initiation of appropriate antibiotic therapy may increase disease morbidity and mortality, especially in patients with septic shock requiring ongoing vasoactive agent support. Therefore, under these circumstances, initiation of antimicrobials should not be postponed for the purpose of performing diagnostic workup. Clinical signs of infection in patients with negative lower respiratory tract cultures should prompt investigation for extrapulmonary sites of infection. By nature, patients managed in an ICU are at risk for several forms of hospital-acquired infection and should be evaluated thoughtfully and broadly. EMPIRICAL THERAPY
Immediate administration of appropriate antibiotic therapy is essential in the treatment of pneumonia. However, antimicrobial treatment is not without risk. In particular, for a patient receiving prolonged broad-spectrum antibiotics, antibiotic pretreatment shows a considerable microbial selection pressure associated with excess mortality. The key decision in initial empirical therapy is determining whether the patient has risk factors for multidrug-resistant (MDR) strains. The distinction between early and late onset pneumonia has classically been used to tailor drug therapy. However, patients admitted after recent hospitalization or from long-term care facilities may also be at increased risk for MDR pathogens. The overall approach to treatment is shown in the algorithm in Fig. 1. INITIAL ANTIBIOTIC SELECTION AND DOSING
Optimal dosing remains a matter of debate. Differences in pharmacokinetics, microbiological characteristics of underlying pathogens, and methodology applied to determine microbial resistance levels all influence the antimicrobial effect of a given dosage. Moreover, penetration into lung tissue is an important factor that should be considered when selecting an antimicrobial regimen. Aminoglycosides are not ideal, because they achieve a lung penetration rate of only 30% to 40%. b-Lactams also have a penetration of less than 50%. Fluoroquinolones, in contrast, show cellular and lung tissue penetration 100% of serum level. Several studies have reported better clinical outcomes using linezolid compared with vancomycin for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, supported by the superior lung penetration of the drug.30
1311
1312
Ottosen & Evans
Fig. 1. Approach to empirical therapy for HAP and VAP.
Differences between spontaneously breathing versus ventilated patients are not firmly settled, and drug-resistant organisms may affect both populations. Therefore, recommendations in these 2 settings are frequently similar. For early onset pneumonia (
