The Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) have collaborated to release a new guideline for the treatment of community-acquired pneumonia (CAP) in adults.1 This new updated guideline is an important achievement because it represents a consensus of both societies. In the past, there were 2 sets of guidelines which were basically similar; however, differences, both real and perceived, between the 2 guidelines had led to some confusion. This joint guideline reduces potential confusion or interpretation now that there is one agreed-upon guideline.
The new guideline incorporates several changes from prior North American guidelines and includes a simpler assessment tool for site-of-care decision, changes in diagnostic recommendations, elimination of a specific time to the first dose of antimicrobial therapy, a simplification of patient stratification (especially for outpatients), shorter course therapy for most patients, and the recognition of the potential for community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) as a cause of CAP (especially of severe CAP).
Although evidence based, the authors of the guideline strongly urge that deviations from these guidelines should not necessarily be considered substandard care, particularly if variance to a recommendation is based on specific patient considerations (eg, known exposure to a specific pathogen or recent travel to an area of endemic infection). I will briefly summarize several of the changes from the prior guideline in this review. Specific recommendations are graded as to the strength of recommendation (weak, moderate, or strong) and the level of evidence (I-III, I being the strongest).
- Severity-of-illness scores, such as the CURB-65, or prognostic models, such as the Pneumonia Severity Index, can be used to identify patients with CAP who may be candidates for outpatient treatment (strong recommendation, level I evidence).
A key decision facing the clinician is whether to hospitalize the patient with CAP. A general consensus is that the majority of patients can be safely treated as outpatients. However, selected patients should be hospitalized based on the requirements of care (ie, need for close observation, respiratory support, intravenous antibiotics, or other concerns). This decision has impact on the extent of diagnostic testing as well as the choice of empirical antimicrobial therapy. The advantages of not hospitalizing patients for CAP are considerable and include decreased cost, patient preference, and avoidance of iatrogenic complications in the hospital. For elder patients, particularly, a reduction in immobilization (ie, time in a hospital bed) time can facilitate better convalescence.
The decision to hospitalize a patient with CAP depends on many variables, including the severity of illness, associated disease, adequacy of home support, and probability of compliance. The admission decision remains a judgmental one; however, prognostic scoring systems have been developed which provide support for this decision.
The prior IDSA guideline (2003) recommended using the "pneumonia prediction rule," which had been developed from studies of the pneumonia Patient Outcomes Research Team and can assist clinicians in making the site-of-care decision. Another scoring system has been added to the new guideline, which recommends an assessment of severity based on the presence 5 easily measurable factors which are listed as an acronym-CURB-65: confusion (based on a specific mental test or disorientation to person, place, or time), urea >7 mmol/L (20 mg/dL), respiratory rate ≥30 breaths/min, blood pressure (systolic <90 mm Hg or diastolic ≤60 mm Hg), and age 65 years or older-as indicators of increased mortality, giving rise to the acronym CURB-65. This acronym promises to be easier to remember and more fully developed than the Pneumonia Severity Index. The 30-day mortality rate for patients with a score of 0 to 1 is 1.5%, and these patients can be treated on an outpatient basis. With a score of 2, the mortality rate rises to 9.2%, and hospital admission is advisable. With a score of 3 or greater, the mortality risk is 22%, and the patient should be admitted to the intensive care unit (ICU).
- Direct admission to an ICU is required for patients with septic shock or with acute respiratory failure requiring intubations and mechanical ventilation (strong recommendation, level II evidence).
- Direct admission to an ICU or high-level monitoring unit is recommended for patients with 3 of the minor criteria for severe CAP listed in Table 1 (moderate recommendation, level II evidence).
A new set of criteria has been developed based on data from individual risks, but keeping the previous ATS criteria format. In addition to the 2 major criteria (need for mechanical ventilation or septic shock), an expanded set of minor criteria (respiratory rate >30 breaths/min, Pao2/Fio2 <250 mm Hg, multilobar infiltrates, confusion, blood urea nitrogen >20 mg/dL, leukopenia resulting from infection, thrombocytopenia, hypothermia, or hypotension requiring aggressive fluid resuscitation) is proposed (Table 1). The presence of at least 3 suggests the need for ICU care but will need prospective validation.
- Blood cultures and sputum are recommended for all ICU patients (strong recommendation, level I evidence).
These tests are considered optional for patients admitted to the general ward. This is another significant change from the prior guideline and is in part based on observational studies that false-positive blood cultures increase the overuse of vancomycin and the hospital stay by approximately 1 day, and blood cultures may have limited benefit for patient with CAP admitted to the general ward. In light of this, the recommendation was changed to focus on patients admitted to the ICU within 24 hours of hospitalization. In these more severely ill patients, a blood culture may increase the likelihood of finding a pathogen not covered by customary treatment. As noted previously, the yield of sputum cultures is variable. Indications for more extensive diagnostic testing include ICU admission for pneumonia, failure of outpatient antibiotic therapy, cavitary infiltrates on presentation, neutropenia, active alcohol abuse, chronic severe liver disease, severe chronic obstructive pulmonary disease, asplenia, recent travel (within 2 weeks), positive rapid Legionella or pneumococcal urinary antigen test, and pleural effusion.
- For patients admitted through the emergency room, the first antibiotic dose should be administered while still in the emergency department (moderate recommendation, level III evidence).
The IDSA/ATS guideline no longer recommends a time window for initiation of antibiotic treatment. Rather than designating a specific window in which to initiate treatment, the committee felt that hospitalized CAP patients should receive the first antibiotic dose in the emergency department. The timing of the first dose has been controversial. The previous recommendation of a relatively narrow 4-hour window to administration of the first dose may have actually been associated with overuse of antimicrobials because clinicians may prescribe them before a firm diagnosis of pneumonia can be established to achieve a high rate of compliance with this recommendation (since it has been a performance measure). For these and other reasons, the committee did not feel that a specific time window for delivery of the first antibiotic dose should be recommended. However, the committee does feel that therapy should be administered as soon as possible after the diagnosis is considered likely.
- A macrolide or doxycycline is recommended for previously healthy individuals who have not received antibiotic therapy within the past 3 months (strong recommend, level I evidence). (The rational here is that the rate of macrolide-resistant Streptococcus pneumoniae is relatively low in this setting of patients, and these agents will cover the large majority of S. pneumoniae as well as the "atypical" pneumonias, Mycoplasma and Chlamydophila, which are common in this group of patients.)
- In outpatients with comorbidities or who have used antibiotics within the previous 3 months, the respiratory fluoroquinolones (moxifloxacin 400 mg QD, gemifloxacin 320 mg QD, levofloxacin 750 mg QD) or a β-lactam plus a macrolide are recommended (strong recommendation, level I evidence). The choice of the preferred regimen is in part based on if there was prior antimicrobial therapy, the alternative choice should be used (ie, if the patient had received a fluoroquinolone within the past 3 months, a β-lactam + macrolide regimen is recommended). (Regarding levofloxacin, the standard dose recommended in this new guideline is 750 mg QD [to be adjusted for renal insufficiency] based on better pharmacodynamic target parameters than the 500-mg QD dose.)
- In regions with a high rate (25%) of infection with high-level macrolide-resistant S. pneumoniae, consider the use of alternative agents listed above for any patient, including those without comorbidities.
For general inpatient treatment, combination therapy with a β-lactam such as cefotaxime, ceftriaxone, ertapenem, or ampicillin-sulbactam, plus azithromycin or monotherapy with a respiratory fluoroquinolone, is recommended (Table 2). For patients with severe CAP requiring ICU admission, recommendations are given based on risks for Pseudomonas and/or CA-MRSA (Table 2). If CA-MRSA is a consideration, linezolid or vancomycin should be added to the regimen. Although methicillin-resistant strains of S.aureus are still the minority, the excess mortality of inappropriate antibiotic therapy would suggest that empirical coverage should be considered when CA-MRSA is a concern. The best indicator of S. aureus is the presence of gram-positive cocci in clusters in a tracheal aspirate or adequate sputum sample. The same findings on preliminary results of blood cultures are not as reliable because of the significant risk of contamination. Clinical risk factors for S. aureus CAP include end-stage renal disease, intravenous drug abuse,prior influenza, and prior antibiotics (especially fluoroquinolones).
- Once the etiology of CAP has been identified based on reliable microbiological methods, antimicrobial therapy should be directed at that pathogen (moderate recommendation, level III evidence).
Treatment options may be simplified if the etiologic agent is established or strongly suspected. Diagnostic procedures that identify a specific etiology within 24 to 72 hours can still be useful for guiding continued therapy. This information is often available at the time of consideration for switch from parenteral to oral therapy and may be used to direct specific oral antimicrobial choices. If, for example, an appropriate culture reveals penicillin-susceptible S. pneumoniae, a narrow-spectrum agent (such as penicillin or amoxicillin) may be used. This will hopefully reduce the selective pressure for resistance.
The major issue with pathogen-specific therapy is management of bacteremic S. pneumoniae CAP. The implications of the observational finding that dual therapy was associated with reduced mortality in bacteremic pneumococcal pneumonia are uncertain. One explanation for the reduced mortality may be the presence of undiagnosed coinfection with an atypical pathogen. An alternative explanation is the immunomodulatory effects of macrolides. It is important to note that these studies evaluated the effects of initial empirical therapy before the results of blood cultures were known and did not examine effects of pathogen-specific therapy after the results of blood cultures were available. The benefit of combination therapy was also most pronounced in the more severely ill patients. Therefore, discontinuation of combination therapy once results of cultures are known is most likely safe in non-ICU patients.
Duration of Therapy
- Patients with CAP should be treated for a minimum of 5 days, should be afebrile for 48 to 72 hours, and should have no more than 1 CAP-associated sign of clinical instability before stopping therapy. Longer duration of therapy may be required for patients who fail initial antimicrobial therapy (moderate recommendation, level II evidence).
Community-acquired pneumonia has traditionally been treated with a 7- to 14-day course of antimicrobial therapy. However, several recent studies have demonstrated that shorter course antibiotic regimens are effective in the treatment of the majority of cases of CAP. Short-term therapy is not recommended for patients with bacteremic S. aureus pneumonia because of the risks for associated endocarditis and deep-seated infection, patients with extrapulmonary infection (especially meningitis), patients with Pseudomonas aeruginosa pneumonia, and patients with infection caused by other less common pathogens. Potential benefits of shorter course therapy include improvement of patient compliance and reduction of microbial resistance, cost, and adverse events such as Clostridium difficile infections.
Additional recommendations which are new since the prior guidelines include the following:
- Patients with CAP who have persistent septic shock despite adequate fluid resuscitation should be considered for treatment with drotrecogin alfa activated within 24 hours of admission (weak recommendation, level II evidence).
- Hypotensive, fluid-resuscitated patients with severe CAP should be screened from occult adrenal insufficiency (moderate recommendation, level II evidence).
- Respiratory hygiene measures, including the use of hand hygiene and masks or tissues for patients with cough, should be used in outpatient settings and emergency departments as a means to reduce the spread of respiratory infections (strong recommendation, level III evidence).