Most initial treatment regimens for hospitalized patients with community-acquired pneumonia (CAP) are empiric. A limited number of pathogens are responsible for the majority of cases．The most commonly detected pathogen is Streptococcus pneumoniae. Other common pathogens include Haemophilus influenzae, the atypical bacteria (Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella spp), oropharyngeal aerobes and anaerobes (in the setting of aspiration), and respiratory viruses. Antibiotics should be started as soon as possible once the diagnosis of bacterial CAP is considered likely.
Despite the use of empiric therapy, testing for a microbial diagnosis is important in clinical or epidemiologic settings suggesting possible infection with an organism that requires treatment different from standard empiric regimens. These include Legionella species, seasonal influenza, avian (eg, H5N1, H7N9) influenza, Middle East respiratory syndrome coronavirus, community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), Mycobacterium tuberculosis, and agents of bioterrorism.
Emerging drug-resistant S. pneumoniae (DRSP) complicates the use of empiric treatment. Treatment failures have been demonstrated with use of macrolides for macrolide-resistant organisms. Most pneumococci respond to higher dose beta-lactams other than cefuroxime.
For hospitalized patients not requiring intensive care unit (ICU) admission, we suggest initial combination therapy with an anti-pneumococcal beta-lactam (ceftriaxone, cefotaxime, ceftaroline, ertapenem, or ampicillin-sulbactam) plus a macrolide (azithromycin or clarithromycin XL), or monotherapy with a respiratory fluoroquinolone (levofloxacin or moxifloxacin) (Grade 1B). We suggest that monotherapy with tigecycline be limited to patients intolerant of beta-lactams and fluoroquinolones (Grade 2B). Coverage for drug-resistant pathogens, such as Pseudomonas or MRSA, should be included in patients with risk factors. Doxycycline may be used as an alternative to a macrolide, especially in patients at high risk of QT interval prolongation. Oral therapy with a macrolide or doxycycline is appropriate only for selected patients without evidence of or risk factors for severe pneumonia.
For hospitalized patients requiring ICU care, we suggest initial combination therapy with an anti-pneumococcal beta-lactam (ceftriaxone, cefotaxime, ceftaroline, or ampicillin-sulbactam) plus either intravenous (IV) therapy with azithromycin or a respiratory fluoroquinolone (levofloxacin or moxifloxacin) plus, if MRSA is suspected, vancomycin (15 mg/kg IV every 12 hours, adjusted to a trough level of 15 to 20 mcg/mL and for renal function; in seriously ill patients, a loading dose of 25 to 30 mg/kg may be given) or linezolid (600 mg IV every 12 hours) (Grade 2B). Coverage for other drug-resistant pathogens, such as Pseudomonas, should be included in patients with risk factors.
For most hospitalized patients who are at substantial risk of morbidity and mortality (eg, Pneumonia Severity Index score IV or V ; CURB-65 score ≥2，we suggest adjunctive glucocorticoids (Grade 2B). We are more likely to give glucocorticoids to more severely ill patients, and we are less likely to give glucocorticoids to patients at increased risk of adverse effects. In patients at elevated risk of adverse effects, clinicians should make the decision about whether to give glucocorticoids on a case-by-case basis. When we give glucocorticoids, we use methylprednisolone 0.5 mg/kg IV every 12 hours for five days. There is limited evidence that infections caused by certain pathogens (eg, influenza virus, Aspergillus spp) may be associated with worse outcomes in the setting of glucocorticoid use; given these concerns, we avoid adjunctive glucocorticoids if one of these pathogens is detected.
We suggest that empiric antimicrobial treatment regimens be modified when results of diagnostic studies indicate a specific pathogen and if coinfection is unlikely based upon clinical or epidemiologic data (Grade 2B).
Patients should demonstrate some improvement in clinical parameters by 72 hours, although fever may persist with lobar pneumonia. Cough from pneumococcal pneumonia may not clear for a week; abnormal chest radiograph findings usually clear within four weeks but may persist for 12 weeks in older individuals and those with underlying pulmonary disease.
We suggest switching from intravenous to oral therapy when patients are hemodynamically stable, demonstrate some clinical improvement (in fever, respiratory status, white blood count), and are able to take oral medications (Grade 2A).
We suggest hospital discharge when the patient is clinically stable from the pneumonia, can take oral medication, has no other active medical problems, and has a safe environment for continued care; we suggest not keeping the patient overnight for observation following the switch (Grade 2B).
Patients with CAP who have a good clinical response within the first two to three days of therapy should generally be treated for five to seven days, but longer treatment is indicated if the initial therapy was not active against the subsequently identified pathogen, if extrapulmonary infection is identified (eg, meningitis or endocarditis) or if the patient has documented P. aeruginosa, S. aureus, or Legionella pneumonia, or pneumonia caused by some less common pathogens. The duration of therapy in these patients should be individualized based upon the clinical response to treatment and patient comorbidities. For the treatment of MRSA pneumonia, we recommend a treatment duration of 7 to 21 days, depending upon the extent of infection and response to therapy; the shorter duration is recommended if the patient has a clear and early clinical response and no evidence of metastatic infection.
Routine follow-up chest radiographs for patients who are responding clinically within the first week are unnecessary. We suggest a follow-up chest radiograph at 7 to 12 weeks after treatment for patients who are over age 50 years to document resolution of the pneumonia and exclude underlying diseases, such as malignancy (Grade 2B). Follow-up chest radiograph is particularly important for males and smokers in this age group.
The most common cause of treatment failure is the lack of response by the host, despite appropriate antibiotics. Risk factors for treatment failure include neoplasia, aspiration pneumonia, neurologic disease, multilobar pneumonia, infection with MRSA, Legionella, or gram-negative bacilli, high Pneumonia Severity Index (PSI) (>90)，antibiotic-resistant pathogen, cavitation, pleural effusion, liver disease, and leukopenia.