1 Define severe community-acquired pneumonia (CAP)

Patients with severe CAP have a number of characteristics:

Unfortunately, it is challenging to prospectively identify this cohort of patients. Of particular concern are patients who are initially triaged as having nonsevere CAP but subsequently need ICU admission (up to 50% of ICU admissions fall under this category in some studies). Such patients tend to have a higher mortality than equally sick patients who have been directly admitted to an ICU. A number of severity of illness scores have been developed to help define severe CAP, a popular one being derived from the joint Infectious Diseases Society of America–American Thoracic Society guidelines for the management of CAP in adults (Box 20-1), which incorporates elements of the confusion, urea, respiratory rate, and blood pressure (CURB) score. By this definition, patients with one major criterion or three minor criteria are designated as having severe CAP. Another widely used score is the Pneumonia Severity Index (PSI). However, none of these scores has been prospectively validated for individual patients. Clinical judgment remains critical; do not blindly follow scores! In recent years other approaches have been explored to identify patients with severe CAP; some of these are discussed below (see answer 9 on recent developments in CAP).

2 Which pathogens most commonly cause severe CAP?

The most common causes of severe CAP in ICU patients are (in order of decreasing incidence):

Pathogens are identified in fewer than 50% of cases. Specific therapy seems to have no particular advantage over empiric therapy except in ICU patients, where every effort should be made to reach an etiologic diagnosis and tailor therapy accordingly. A typical work-up for an ICU patient would include sputum Gram stain in addition to sputum and blood cultures. In addition urinary antigen tests for Legionella and pneumococcus should be considered. More invasive tests, such as bronchoscopic bronchoalveolar lavage, may be considered in individual patients.

3 How is CAP diagnosed? Are the sputum Gram stain and culture diagnostically helpful for CAP?

CAP is diagnosed on the basis of the presence of a constellation of signs and symptoms (fever, cough, sputum production, and pleuritic chest pain) with radiographic evidence of lung infiltrates. Sputum Gram stain and culture can be obtained noninvasively and are inexpensive diagnostic tests. A sputum Gram stain specimen is considered satisfactory for interpretation when the neutrophil count is ≥ 25 and the epithelial cell count is ≤ 10 per low power field. Gram staining can have multiple benefits: the results can be used to broaden coverage to cover microorganisms that are typically not covered by empiric regimens, such as S. aureus and GNRs. Conversely, the absence of characteristic Gram stains and sputum culture is a strong argument for presumptively excluding S. aureus and GNRs as probable etiologies for the pneumonia. In addition, a positive Gram stain validates a subsequent sputum culture. Keep in mind the diagnostic limitations of sputum Gram stain and culture, including the inability to visualize atypical organisms, contamination by oral flora, and the difficulty encountered by some patients to provide adequate specimens.

4 What determines the selection of empiric antimicrobial therapy for patients with severe CAP?

The initial empiric antibiotic regimen for patients in the ICU with severe CAP is outlined in Box 20-2. Broadly speaking, the general principles of antibiotic therapy are as follows:

5 What risk factors would prompt broader coverage?

Risk factors that would prompt broader antimicrobial coverage can be conveniently considered by the type of organism to be covered:

6 When should antibiotics be initiated, and what is the optimal duration of treatment?

Although earlier guidelines recommended initiation of antibiotics within 4 hours of diagnosis of CAP, more recent evidence has prompted a subtle shift in the current guidelines. They still recommend prompt initiation of antibiotics but do not specify a window of greatest benefit. The guidelines do recommend that patients admitted through the emergency department (ED) should receive their first dose of antibiotics while in the ED.

Patients with CAP should be treated for a minimum of 5 days, should be afebrile for 48 to 72 hours, and should not have more than one CAP-associated sign of clinical instability (Box 20-3) before stopping treatment.

7 When is it safe to switch a patient to oral therapy?

Conversion to oral therapy may be considered in the hemodynamically stable patient who is improving clinically, can take oral medications, and has a normally functioning gastrointestinal tract.

8 Discuss CA-MRSA infections

An important trend in public health is the increasing prevalence of CA-MRSA infections. Here we will briefly discuss some of the salient features caused by CA-MRSA, particularly with reference to CAP.

9 What are some recent developments in CAP?

Areas of active investigation in the field include biomarkers for the diagnosis and prognosis in CAP, using the genomic bacterial load as a marker of disease severity, and epidemiologic studies of long-term health effects of CAP. These will be briefly discussed.

10 What defines a treatment failure?

The majority of patients receiving appropriate therapy show a favorable clinical response within 72 hours. Therefore initial antibiotic therapy should not be changed before 72 hours unless indicated by significant clinical worsening or microbiologic data. Remember that certain host factors, such as advanced age, alcoholism, and chronic obstructive pulmonary disease, have been associated with delayed resolution despite appropriate treatment. Radiographic resolution of pneumonia lags behind clinical improvement and in some cases may take up to 8 to 10 weeks to clear completely.

11 Discuss the potential reasons why a patient may not respond favorably to empiric therapy

Clinical deterioration or a lack of response to empiric antimicrobial therapy within 3 days often indicates treatment failure, warranting thorough reassessment and additional investigation. The following should be considered:

12 How should a patient with nonresolving pneumonia be evaluated?

The clinician should review initial culture results and sensitivities and collect additional lower respiratory tract and blood cultures. Broadening empiric therapy may be indicated while awaiting results of additional testing. All patients should have a repeated chest radiograph at this time. Additional history may reveal HIV risk factors, tick exposure, travel history, or other diagnostic clues. Further testing, such as a chest computed tomographic or ultrasound scan, should be directed at the likely cause of treatment failure. If the procedure can be performed safely, a thoracentesis of a pleural effusion can exclude a complicated effusion or empyema. Bronchoscopy has good diagnostic utility, and specimens should be sent for quantitative bacterial cultures and sensitivities, as well as for stains and cultures of unusual organisms (mycobacteria, viruses, endemic fungi, and P. jiroveci). If the diagnosis remains elusive, a trial of corticosteroids or a thoroscopic or open lung biopsy may be considered in the appropriate clinical setting.

13 Which noninfectious processes can present with signs and symptoms of acute pneumonia?

Noninfectious conditions that can mimic acute pneumonia include ARDS, traumatic pulmonary contusion, pneumonitis resulting from connective tissue disease (e.g., systemic lupus erythematosus), acute hypersensitivity pneumonitis, drug-induced pneumonitis, diffuse alveolar hemorrhage (e.g., Goodpasture syndrome), Wegener granulomatosis, bronchiolitis obliterans organizing pneumonia, acute interstitial pneumonia (Hamman-Rich syndrome), acute eosinophilic pneumonia, pulmonary embolism with infarction, atelectasis, chemical pneumonitis (aspiration), and malignancy (e.g., bronchoalveolar carcinoma, lymphangitic carcinomatosis, Kaposi sarcoma).

14 What are hospital-acquired pneumonia (HAP), health care–associated pneumonia (HCAP), and ventilator-associated pneumonia (VAP)?

The use of clinical criteria alone without microbiologic data tends to overdiagnose lung infection.

15 How do you decide on the initial empiric antibiotic therapy for HAP, HCAP, or VAP?

If the patient has late-onset pneumonia development (≥ 5 days) or risk factors for MDR pathogens, then broad-spectrum antibiotic therapy is indicated. If neither of these criteria is met, limited-spectrum antibiotic therapy is appropriate. If HAP, VAP, or HCAP is suspected, disease severity is not considered in the initial empiric antibiotic decision.

16 What are the risk factors for MDR pathogens causing HAP, HCAP, and VAP?

Risk factors for MDR causing HAP, HCAP, and VAP include antimicrobial therapy in the preceding 90 days, current hospitalization of 5 days or more, high frequency of antibiotic resistance in the community or in the specific hospital unit, immunosuppressive disease and/or therapy, or presence of risk factors for HCAP (hospitalization for 2 days or more in the preceding 9 days, residence in a nursing home or extended-care facility, home infusion therapy [including antibiotics], long-term dialysis within 30 days, home wound care, family member with MDR pathogen).

17 What initial empiric antibiotic therapy is recommended for HAP, HCAP, or VAP in patients with no known risk factors for MDR, early onset pneumonia development, and any disease severity?

Recommended antibiotics include ceftriaxone, levofloxacin (moxifloxacin or ciprofloxacin can replace levofloxacin), ampicillin-sulbactam, or ertapenem. Potential pathogens include S. pneumoniae, H. influenzae, methicillin-sensitive S. aureus, and antibiotic-sensitive enteric gram-negative bacilli (Escherichia coli, Klebsiella pneumoniae, Enterobacter, Proteus, Serratia marcescens.

18 What initial empiric antibiotic therapy is recommended for HAP, HCAP, or VAP in patients with known risk factors for MDR, late-onset disease development, and any disease severity?

Recommended combination antibiotic therapy includes an antipseudomonal cephalosporin (cefepime or ceftazidime), antipseudomonal carbapenems (imipenem or meropenem), or β-lactam–β-lactamase inhibitor (piperacillin-tazobactam) plus an antipseudomonal fluoroquinolone (ciprofloxacin or levofloxacin) or an aminoglycoside (amikacin, gentamicin, or tobramycin). Linezolid or vancomycin should be added if MRSA risk factors are present or there is a high incidence locally. Potential MDR pathogens include P. aeruginosa, K. pneumoniae, Acinetobacter species, and MRSA (Table 20-1).

^{Table 20-1} Initial Empiric Therapy for HAP, VAP, and HCAP: for Patients with Late-Onset Disease or Risk Factors for MDR Pathogens and All Disease Severity

ESBL, Extended-spectrum β-lactamase.

^* If an ESBL⁺ strain, such as K. pneumoniae, or an Acinetobacter species is suspected, a carbapenem is a reliable choice. If L. pneumophila is suspected, the combination antibiotic regimen should include a macrolide (e.g., azithromycin), or a fluoroquinolone (e.g., ciprofloxacin or levofloxacin) should be used rather than an aminoglycoside.

^† If MRSA risk factors are present or there is a high incidence locally.

Modified from American Thoracic Society, Infectious Diseases Society of America: Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 171:388-416, 2005.

19 What are some specific treatment strategies for MDR Pseudomonas, Acinetobacter, and MRSA VAP?

20 What measures can be taken to decrease the risk of VAP?

21 How do you decide when to continue, de-escalate, and discontinue the use of antibiotic treatment on the basis of clinical response and culture data?

When HAP, VAP, or HCAP is suspected, consider obtaining lower respiratory tract samples for culture (quantitative or semiquantitative) and microscopy. Unless there is both a low clinical suspicion for pneumonia and negative microscopy of the lower respiratory tract sample, begin empiric antimicrobial therapy. At day 2 and 3, check cultures and assess clinical response (temperature, white blood cell [WBC] count, chest radiograph, oxygenation, purulent sputum, hemodynamic changes, and organ function). If no clinical improvement is seen after 2 to 3 days with negative cultures, search for other pathogens, complications, diagnoses, or sites of infection. If no improvement is seen but cultures are positive, adjust antibiotic therapy but also broaden infectious search as you would with negative cultures. If clinical improvement is noted after 2 to 3 days but cultures are negative, consider stopping antibiotics. If clinical improvement is noted and cultures are positive, de-escalate antibiotics, and consider treating selected patients for 7 to 8 days and reassess (Fig. 20-1).

Figure 20-1 Algorithm for treatment of HAP, VAP, or HCAP.

Data from American Thoracic Society, Infectious Diseases Society of America: Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 171:388-416, 2005.

22 How long should you continue antibiotic management for HAP, HCAP, or VAP?

In a prospective, randomized clinical trial, an 8-day treatment strategy for culture-proved VAP resulted in a significant decrease in multiresistant bacteria and more antibiotic-free days with no differences in mortality, ICU length of stay, or mechanical ventilator–free days when compared with a 15-day regimen. A higher rate of recurrence was documented with the 8-day regimen when the infection was due to Acinetobacter or Pseudomonas; therefore VAP due to these organisms should be treated for 15 days. Because the infecting pathogens are similar, HAP and HCAP can be treated similarly. Extended therapy (14-21 days) may be indicated in the setting of multilobar disease, cavitation, malnutrition, or necrotizing gram-negative infection.