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Treatment of community-acquired pneumonia in adults who require hospitalization
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2012. | This topic last updated: Oct 15, 2011.

INTRODUCTION — Community-acquired pneumonia (CAP) is defined as an acute infection of the pulmonary parenchyma in a patient who has acquired the infection in the community, as distinguished from hospital-acquired (nosocomial) pneumonia (HAP). A third category of pneumonia, designated healthcare-associated pneumonia, (HCAP) is acquired in other healthcare facilities, such as nursing homes, dialysis centers, and outpatient clinics.

CAP is a common and potentially serious illness. It is associated with considerable morbidity and mortality, particularly in elderly patients and those with significant comorbidities [1,2]. (See "Prognosis of community-acquired pneumonia in adults".)

The treatment of CAP in adults who require hospitalization will be reviewed here. A variety of other important issues related to CAP are discussed separately. These include:

INDICATIONS FOR HOSPITALIZATION — Determination of whether a patient with community-acquired pneumonia (CAP) can be treated safely as an outpatient or requires hospitalization is essential before selecting an antibiotic regimen. Severity of illness is the most critical factor in making this determination, but other factors should also be taken into account. These include ability to maintain oral intake, likelihood of compliance, history of substance abuse, cognitive impairment, living situation, and patient functional status. These issues with appropriate references are discussed in detail elsewhere. (See "Community-acquired pneumonia in adults: Risk stratification and the decision to admit".)

Summarized briefly, prediction rules have been developed to assist in the decision of site of care for CAP. The two most commonly used prediction rules are the Pneumonia Severity Index (PSI) and CURB-65. The PSI is better studied and validated, but requires a more complicated assessment (calculator 1).

CURB-65 uses five prognostic variables:

  • Confusion (based upon a specific mental test or disorientation to person, place, or time)
  • Urea (blood urea nitrogen in the United States) >7 mmol/L (20 mg/dL)
  • Respiratory rate >30 breaths/minute
  • Blood pressure [BP] (systolic <90 mmHg or diastolic <60 mmHg)
  • Age >65 years

The authors of the original CURB-65 report suggested that patients with a CURB-65 score of 0 to 1, who comprised 45 percent of the original cohort and 61 percent of the later cohort, were at low risk and could probably be treated as outpatients. Those with a score of 2 should be admitted to the hospital, and those with a score of 3 or more should be assessed for care in the intensive care unit (ICU), particularly if the score was 4 or 5 (calculator 2).

A simplified version (CRB-65), which does not require testing for blood urea nitrogen, may be appropriate for decision-making in primary care practitioners' offices. With either version, admission to the hospital is recommended if one or more points are present.

Other severity scoring systems have been developed that focus on severe CAP, such as SMART-COP [3] and the Severe CAP (SCAP) score [4]; there is less experience with these scoring systems compared to the other systems described above (See "Community-acquired pneumonia in adults: Risk stratification and the decision to admit", section on 'Admission to intensive care' and "Community-acquired pneumonia in adults: Risk stratification and the decision to admit", section on 'Severe community-acquired pneumonia score'.)

Clinical judgment should be used for all patients, incorporating the prediction rule scores as a component of the decision for hospitalization or ICU admission, but not as an absolute determinant [5]. Limitations in the PSI scoring are the complexity of the system, and the failure to account for comorbidities and social factors, such as homelessness, for making site of care decisions [6-8].

PRINCIPLES OF ANTIMICROBIAL THERAPY — Community-acquired pneumonia (CAP) can be caused by a variety of pathogens, with bacteria being the most common identifiable cause (table 1 and table 2 and figure 1) [2,9,10]. The predominant pathogen is Streptococcus pneumoniae. Other common pathogens include Haemophilus influenzae , the atypical bacteria (Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella spp), oropharyngeal aerobes and anaerobes (in the setting of aspiration), and respiratory viruses. A randomized trial and a retrospective study have suggested that Staphylococcus aureus is increasing as a cause of CAP requiring admission to the hospital (some are due to community-associated methicillin-resistant S. aureus strains) [11,12]. Gram-negative bacilli (Enterobacteriaceae and Pseudomonas aeruginosa) are the cause of CAP in some patients. The frequency of other causes, such as Mycobacterium tuberculosis, Chlamydophila psittaci (cause of psittacosis), C. burnetii (cause of Q fever), and endemic fungi vary in different epidemiologic settings.

Studies utilizing molecular diagnostic methods have reported the rate of detection of a viral etiology in patients with CAP at approximately 30 percent; influenza has been identified in many of these patients (table 1 and figure 1) [13,14]. The rate of mixed viral-bacterial infection is approximately 20 percent; such mixed infections have been found to be associated with more severe CAP and longer hospitalization than CAP caused by bacteria alone [15]. (See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'Viruses'.)

The choice of initial therapy is complicated by the emergence of antibiotic resistance among S. pneumoniae, the most common bacterium responsible for CAP as well as concern for MRSA in severe CAP. (See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'Microbiology' and "Antibiotic studies for the treatment of community-acquired pneumonia in adults", section on 'Drug resistance and choice of therapy'.)

Empiric therapy — Antibiotic therapy is typically begun on an empiric basis, since the causative organism is not identified in an appreciable proportion of patients (table 1 and table 2) [2,16]. In addition, the clinical features and chest radiographic findings are not sufficiently specific to determine etiology and influence treatment decisions. The Gram stain of respiratory secretions can be useful for directing the choice of initial therapy if performed on a good quality sputum sample and interpreted by skilled examiners using appropriate criteria [2]. (See "Diagnostic approach to community-acquired pneumonia in adults", section on 'Sputum'.)

Benefit from a pathogen-directed approach to treatment, particularly for moderate to severe CAP, may emerge as rapid diagnostic tests become more widely available. However, there has been some concern that narrowing the coverage spectrum of antibiotics when a specific pathogen is identified may undertreat patients who have concurrent infection with atypical organisms.

This concern was not borne out in a prospective randomized trial comparing pathogen-directed treatment (PDT) and empiric broad-spectrum antibiotic treatment (EAT) in 262 hospitalized patients with CAP [17]. PDT was based upon microbiologic studies (rapid diagnostic tests) or clinical presentation; EAT patients received a beta-lactam/beta-lactamase inhibitor plus erythromycin or, if admitted to the intensive care unit (ICU), ceftazidime and erythromycin. Overall, clinical outcomes (length of stay, 30 day mortality, fever resolution, and clinical failure) were the same for both groups. Adverse events were more frequent in the EAT group, but were primarily related to the specific antimicrobial choice (ie, erythromycin).

Despite the general 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, influenza A and B or avian influenza, community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), or agents of bioterrorism. (See "Diagnostic approach to community-acquired pneumonia in adults" and "Sputum cultures for the evaluation of bacterial pneumonia", section on 'Community-acquired pneumonia'.)

The selection of antimicrobial regimens for empiric therapy is based upon a number of factors, including:

Additional factors that may affect the choice of antimicrobial regimen include the potential for inducing antimicrobial resistance, pharmacokinetic and pharmacodynamic properties, safety profile, and cost [18].

The effectiveness of empiric antimicrobial regimens may be decreased by the emergence of newly recognized pathogens, such as CA-MRSA. (See "Epidemiology of methicillin-resistant Staphylococcus aureus infection in adults", section on 'Community-associated methicillin-resistant Staphylococcus aureus'.)

Common pathogens — Although a variety of bacterial pathogens can cause CAP, a limited number are responsible for the majority of cases. (See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'Microbiology'.)

With respect to patients who require hospitalization but not admission to an ICU, the most frequently isolated pathogens are S. pneumoniae, respiratory viruses (eg, influenza, parainfluenza, respiratory syncytial virus), and, less often, M. pneumoniae, H. influenzae, C. pneumoniae, and Legionella (table 2).

The distribution is different in patients with CAP who require admission to an ICU. S. pneumoniae is most common but Legionella, gram-negative bacilli, Staphylococcus aureus, and influenza are also important (table 2). Community-associated MRSA typically produces a necrotizing pneumonia with high morbidity and mortality. (See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'S. aureus'.)

Risk factors for CAP due to gram-negative bacilli include previous antibiotic therapy, immunosuppression, pulmonary comorbidity (eg, cystic fibrosis, bronchiectasis, or repeated exacerbations of chronic obstructive pulmonary disease that require frequent glucocorticoid and/or antibiotic use), probable aspiration, and multiple medical comorbidities (eg, diabetes mellitus, alcoholism) [2,18,19]. (See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'Gram-negative bacilli'.)

The 2007 Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines on the management of CAP recommend empiric antibiotic therapy directed against P. aeruginosa in patients with gram-negative bacilli on Gram stain, since such a regimen will also cover other gram-negative bacilli, such as Klebsiella pneumoniae [2]. (See "Pseudomonas aeruginosa pneumonia" and "Overview of Klebsiella pneumoniae infection", section on 'Community-acquired pneumonia'.)

Risk factors for drug resistance — Risk factors for and other issues related to drug resistance in patients with CAP are discussed in detail elsewhere. (See "Antibiotic studies for the treatment of community-acquired pneumonia in adults", section on 'Drug resistance and choice of therapy'.)

Summarized briefly, risk factors for drug-resistant S. pneumoniae in adults include:

  • Age >65 years
  • Beta-lactam, macrolide, or fluoroquinolone therapy within the past three to six months
  • Alcoholism
  • Medical comorbidities
  • Immunosuppressive illness or therapy
  • Exposure to a child in a day care center

Recent therapy or a repeated course of therapy with beta-lactams, macrolides, or fluoroquinolones are risk factors for pneumococcal resistance to the same class of antibiotic.

The impact of discordant drug therapy, which refers to treatment of an infection with an antimicrobial agent to which the causative organism has demonstrated in vitro resistance, appears to vary with antibiotic class and possibly with specific agents within a class. Most studies have been performed in patients with S. pneumoniae infection and suggest that current levels of beta-lactam resistance generally do not cause treatment failure when appropriate agents (eg, amoxicillin, ceftriaxone, cefotaxime) and doses are used. Cefuroxime is a possible exception with beta-lactams and there appears to be an increased risk of macrolide failure in patients with macrolide-resistant S. pneumoniae. (See "Antibiotic studies for the treatment of community-acquired pneumonia in adults", section on 'Outcomes with discordant drug therapy'.)

GUIDELINES — A number of medical societies have issued guidelines for the treatment of community-acquired pneumonia (CAP) [2,20,21]. The antibiotic regimens advocated by a collaboration between the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) in 2007 [2] and the British Thoracic Society (BTS) in 2009 [20] are summarized in Tables 3 and 4, respectively (table 3 and table 4).

The following discussion will review antibiotic therapy in patients with CAP who require hospitalization. Guideline recommendations for therapy in patients with CAP treated in the outpatient setting are presented separately. (See "Treatment of community-acquired pneumonia in adults in the outpatient setting".)

In studies from different regions of the world, atypical pathogens account for 20 to 30 percent of cases of CAP in hospitalized patients [22]. However, the value of providing empiric coverage for atypical pathogens (eg, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila) is unclear. One reason for this is that testing for M. pneumoniae and C. pneumoniae is not usually done, and there are no United States Food and Drug Administration (FDA)-cleared tests to detect them in adults. Thus, their role in an individual case or in population-based studies is not well elucidated.

The issue of coverage of atypical bacteria was addressed in a meta-analysis of 24 randomized trials of over 5000 patients with CAP requiring hospitalization; most trials compared fluoroquinolone monotherapy to non-atypical monotherapy [23]. There was no significant difference in mortality (RR 1.13, 95% CI 0.82-1.54) or adverse effects between the atypical arm and non-atypical arm. There was a nonsignificant trend toward clinical success when treatment covered atypical bacteria, a difference that disappeared when only methodologically high quality trials were evaluated. Clinical success was significantly higher in the atypical arm for Legionella pneumophila. The trials were not designed to compare the time to response with different regimens.

An international observational study of over 4300 hospitalized patients with CAP published after the meta-analysis found that antimicrobial regimens with atypical coverage, compared to regimens that did not have atypical coverage, were associated with significant reductions in time to clinical stability (3.2 versus 3.7 days), length of stay in hospital (6.1 versus 7.1 days), and CAP-related mortality (3.8 versus 6.4 percent) [22].

A well-designed prospective trial is required to more definitively determine the need to cover atypical pathogens in empiric regimens for CAP requiring hospitalization [23].

TREATMENT REGIMENS — Antibiotic recommendations for hospitalized patients with community-acquired pneumonia (CAP) are divided by the site of care (intensive care unit [ICU] or non-ICU). Most hospitalized patients are initially treated with an intravenous regimen. However, many patients without risk factors for severe pneumonia can be treated with oral therapy, especially with highly bioavailable agents such as the fluoroquinolones [24].

Hospitalized patients with CAP are initially treated with empiric antibiotic therapy. When the etiology of CAP has been identified based upon reliable microbiologic methods, and there is no laboratory or epidemiologic evidence of coinfection, treatment regimens may be simplified and directed to that pathogen. The results of diagnostic studies that provide identification of a specific etiology within 24 to 72 hours can be useful for guiding continued therapy. (See "Diagnostic approach to community-acquired pneumonia in adults".)

Pathogen-specific therapy is discussed separately (table 5). (See "Pneumococcal pneumonia in adults" and "Mycoplasma pneumoniae infection in adults" and "Pneumonia caused by Chlamydophila (Chlamydia) pneumoniae in adults" and "Treatment and prevention of Legionella infection" and "Pseudomonas aeruginosa pneumonia" and "Overview of Klebsiella pneumoniae infection" and "Treatment of seasonal influenza in adults".)

Pneumonia in patients admitted to the hospital from long-term care facilities is not considered community-acquired. It is categorized as healthcare-associated pneumonia (HCAP), and is discussed separately. (See "Epidemiology, pathogenesis, microbiology, and diagnosis of hospital-acquired, ventilator-associated, and healthcare-associated pneumonia in adults" and "Important sites and pathogens causing infections in long term care facilities".)

Not in the ICU — For patients admitted to a general ward, we suggest one of the following regimens (table 3):

  • Combination therapy with ceftriaxone (1 to 2 g IV daily), cefotaxime (1 to 2 g IV every eight hours), ceftaroline (600 mg IV every 12 hours), ertapenem (1 g IV daily), or ampicillin-sulbactam (1.5 to 3 g IV every six hours) plus a macrolide (azithromycin [500 mg IV or orally daily] or clarithromycin XL [two 500 mg tablets once daily]). Doxycycline (100 mg orally or IV twice daily) may be used as an alternative to a macrolide. Oral therapy with a macrolide or doxycycline is appropriate only for selected patients without evidence of or risk factors for severe pneumonia.
  • Monotherapy with a respiratory fluoroquinolone given either IV or orally except as noted (levofloxacin 750 mg daily or moxifloxacin 400 mg daily or gemifloxacin 320 mg daily [only available in oral formulation]).
  • Monotherapy with tigecycline, particularly as an alternative for patients with beta-lactam intolerance.

If the patient has risk factors for drug-resistant pathogens, such as Pseudomonas or MRSA, coverage for these organisms should be included, as discussed in the following section. Patients with necrotizing or cavitary infiltrates or empyema should also be treated empirically for MRSA [25].

When aspiration pneumonia is suspected, it is important to cover oral anaerobes. This is discussed in detail separately. (See "Aspiration pneumonia in adults", section on 'Treatment'.)

Admitted to an ICU

Empiric therapy — Patients requiring admission to an ICU are more likely to have risk factors for resistant pathogens, including community-associated MRSA and Legionella spp.

  • In patients without risk factors for or microbiologic evidence of Pseudomonas aeruginosa or MRSA, we recommend intravenous combination therapy with a potent anti-pneumococcal beta-lactam (ceftriaxone 1 to 2 g daily, cefotaxime 1 to 2 g every eight hours, or ampicillin-sulbactam 1.5 to 3 g every six hours) PLUS either an advanced macrolide (azithromycin 500 mg daily) or a respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) (table 3). Although the optimal doses of the beta-lactams (ceftriaxone, cefotaxime, ampicillin-sulbactam) have not been studied adequately, we favor the higher doses, at least initially, until the minimum inhibitory concentrations against possible isolates (eg, Streptococcus pneumoniae) are known.

  • In patients (particularly those with bronchiectasis or COPD and frequent antimicrobial or glucocorticoid use) who may be infected with Pseudomonas aeruginosa or other resistant pathogens, therapy should include agents effective against the pneumococcus, P. aeruginosa, and Legionella spp. Acceptable regimens include combination therapy with a beta-lactam antibiotic and a fluoroquinolone, such as the following regimens:

  • For penicillin-allergic patients, the type and severity of reaction should be assessed. The great majority of patients who are allergic to penicillin by skin testing can still receive cephalosporins (especially third-generation cephalosporins) or carbapenems. If there is a history of a mild reaction to penicillin (not an IgE-mediated reaction, Stevens Johnson syndrome or toxic epidermal necrolysis), it is reasonable to administer a cephalosporin or carbapenem using a simple graded challenge (eg, give 1/10 of dose, observe closely for 1 hour, then give remaining 9/10 of dose, observe closely for 1 hour). Skin testing is indicated in some situations. For penicillin-allergic patients, if a skin test is positive or if there is significant concern to warrant avoidance of a cephalosporin or carbapenem, options include: aztreonam (2 g IV every 6 to 8 hours) plus levofloxacin (750 mg daily); or aztreonam plus moxifloxacin plus an aminoglycoside. Indications and strategies for skin testing are reviewed elsewhere. (See "Penicillin-allergic patients: Use of cephalosporins, carbapenems, and monobactams".)
  • Patients with past allergic reactions to cephalosporins may be treated with aztreonam (2 g IV every 6 to 8 hours), with the possible exception of those allergic to ceftazidime. Ceftazidime and aztreonam have similar side chain groups, and cross reactivity between the two drugs is variable. The prevalence of cross-sensitivity has been estimated at <5 percent of patients, based upon limited data. Patients with past reactions to ceftazidime that were life-threatening or suggestive of anaphylaxis (involving urticaria, bronchospasm, and/or hypotension) should not be given aztreonam unless evaluated by an allergy specialist. In contrast, a reasonable approach in those with mild past reactions to ceftazidime (eg, uncomplicated maculopapular rash) would involve informing the patient of the low risk of cross-reactivity and administering aztreonam with a graded challenge (1/100, 1/10, full dose, each separated by 1 hour of observation). (See "Cephalosporin-allergic patients: Subsequent use of cephalosporins and related antibiotics", section on 'Use of carbapenems and monobactams'.)

The fluoroquinolones may be administered orally when the patient is able to take oral medications. The dose of levofloxacin is the same when given intravenously and orally, while the dose of ciprofloxacin is 750 mg orally twice daily.

  • Empiric therapy for CA-MRSA should be given to hospitalized patients with severe CAP, as defined by any of the following: admission to the ICU, necrotizing or cavitary infiltrates, or empyema [25]. We also suggest empiric therapy of MRSA in patients with severe CAP who have risk factors for community-acquired (CA)-MRSA (recent antimicrobial therapy or recent influenza-like illness). In such patients, we recommend treatment for MRSA with the addition of vancomycin (15 mg/kg IV every 12 hours, adjusted for renal function) or linezolid (600 mg IV twice daily) until the results of culture and susceptibility testing are known. Clindamycin (600 mg IV or orally three times daily) may be used as an alternative to vancomycin or linezolid if the isolate is known to be susceptible. Ceftaroline is active against most strains of MRSA, but is not FDA-approved for pneumonia caused by S. aureus. Linezolid may be given orally when the patient is able to receive oral medications. If MRSA is not isolated, coverage for this organism should be discontinued.

CA-MRSA — As discussed above, strong consideration should be given for empiric treatment for CA-MRSA with vancomycin or linezolid in hospitalized patients with severe CAP. Although data regarding the therapy of pneumonia caused by CA-MRSA are limited, a randomized trial showed superiority in clinical outcomes, but not mortality, of linezolid compared with vancomycin in nosocomial pneumonia caused by MRSA [26]. The treatment of MRSA pneumonia is discussed in detail separately. (See "Treatment of hospital-acquired, ventilator-associated, and healthcare-associated pneumonia in adults", section on 'Methicillin-resistant Staphylococcus aureus'.)

Although community-acquired MRSA (CA-MRSA) is typically susceptible to more antibiotics than hospital-acquired MRSA, it appears to be more virulent [27]. This strain is known as “USA 300.” The gene for Panton Valentine Leukocidin (PVL) characterizes this strain. CA-MRSA often causes a necrotizing pneumonia associated with PVL and other toxin production, although the exact role of the various virulence factors remains controversial [28-33]. Vancomycin does not decrease toxin production, whereas linezolid has been shown to reduce toxin production in experimental models [34,35]. However, one study of patients with hospital-acquired pneumonia (HAP) due to MRSA observed the severity of infection and clinical outcome was not influenced by the presence of the PVL gene [36]. (See "Treatment of invasive methicillin-resistant Staphylococcus aureus infections in adults".)

One concern with vancomycin is the increasing MICs of MRSA that have emerged in recent years, which may reduce the efficacy of vancomycin in pulmonary infection. When vancomycin is used, trough concentrations should be monitored in order to ensure that a target trough concentration between 15 and 20 mcg/mL is achieved. There may be important differences in potency and toxicity based on the supply source of generic formulations of vancomycin [37]. (See "Vancomycin dosing and serum concentration monitoring in adults".)

CA-MRSA as the cause of CAP should be suspected when pneumonia develops in a person known to be colonized with CA-MRSA or in those with risk factors for CA-MRSA colonization (eg, contact sport participants, injection drug users, those living in crowded conditions, men who have sex with men, prisoners). CA-MRSA pneumonia should also be suspected in young, previously healthy adults with a recent influenza-like illness or if the course is fulminant, imaging shows pulmonary necrosis or empyema and/or the sputum Gram stain shows gram-positive cocci in clusters.

Factors associated with rapid mortality include infection with influenza, the need for ventilator or inotropic support, onset of respiratory distress syndrome, hemoptysis, and leukopenia. In a report of 51 cases of CAP caused by Staphylococcus aureus (79 percent of which were MRSA), 39 percent had a WBC count <4000/microL, and this finding was associated with a poor prognosis. In contrast, a WBC >10,000/microL appeared to be protective [38].

If a sputum culture reveals methicillin-susceptible Staphylococcus aureus (MSSA), therapy should be changed to nafcillin (2 g IV every four hours) or oxacillin (2 g IV every four hours) (table 5).

Fluoroquinolone monotherapy — The role of monotherapy with a respiratory fluoroquinolone has not been established for severe CAP. In an observational study of 270 patients with CAP and shock, the 58 percent treated with combination antibiotic therapy (with a third-generation cephalosporin and a macrolide) had a significantly higher 28-day in-ICU survival than the 42 percent who received fluoroquinolone monotherapy (HR 1.69, 95% CI 1.09-2.60) [39]. Survival was not different comparing combination and monotherapy in ICU patients without shock. If the patient has pneumococcal meningitis, monotherapy with a fluoroquinolone is not recommended. (See "Treatment of bacterial meningitis caused by specific pathogens in adults", section on 'Streptococcus pneumoniae'.)

Macrolide-containing regimens — Observational studies have suggested that combination regimens containing a macrolide plus a beta-lactam may result in better clinical outcomes in patients with severe CAP, especially bacteremic pneumococcal pneumonia; this is likely due to the immunomodulatory effects of macrolides [40-43]. Randomized controlled trials should ideally be performed to clarify this issue, but this will be logistically difficult to do.

Influenza therapy — Antiviral treatment is recommended as soon as possible for all persons with suspected or confirmed influenza requiring hospitalization or who have progressive, severe, or complicated illness, regardless of previous health or vaccination status [44]. (See "Treatment of seasonal influenza in adults".)

Other agents — Other antibiotics that have been studied and approved by the FDA for the treatment of CAP include ceftaroline and tigecycline [45,46]. Studies of these, and other, agents are presented separately. (See "Antibiotic studies for the treatment of community-acquired pneumonia in adults".)

Timing of antimicrobial initiation — The benefit of prompt initiation of antimicrobial therapy has been evaluated, with more recent findings questioning if this is an independent risk factor for outcome:

  • In a retrospective study of 13,771 Medicare patients, antibiotic administration within four hours of hospital arrival was associated with reductions in mortality (6.8 compared to 7.4 percent with delay in antibiotics) and length of stay (0.4 days shorter) [47].
  • A retrospective study of 603 patients with CAP at a single academic center found no difference in the time to clinical stability between those who received antibiotics within four hours and those whose treatment was later [48].
  • The time to first antibiotic dose was not independently associated with mortality in an observational study of 451 CAP patients from another tertiary center [49]. Delay in antibiotics was more common in patients with an altered mental status or signs of sepsis. Time to first antibiotic dose was possibly a marker of comorbidities driving both an atypical presentation and mortality rather than directly contributing to the outcome. Diagnostic uncertainty led to delay of initial antimicrobial therapy in another study [50].
  • A retrospective study of 548 patients found that when the required time to first antibiotic dose changed from eight hours to four hours, a reduction in the accuracy of the initial diagnosis of CAP occurred, although the mean time to first antibiotic dose was similar in both groups [51].

The United States National Pneumonia Medicare Quality Improvement Project and the National Quality Forum have changed the recommended target for initial administration of antimicrobial therapy from four to six hours after arrival at the hospital [52-54]. The previously recommended four hour window resulted in the unintended consequence of overuse of antimicrobials before the diagnosis of pneumonia could be definitively established, and there was no significant difference in outcome when the delay was six hours rather than four hours [53,55,56].

Clinical response to therapy — With appropriate antibiotic therapy, some improvement in the patient's clinical course is usually seen within 48 to 72 hours (table 6). Patients who do not demonstrate some clinical improvement within 72 hours are considered nonresponders. (See 'The nonresponding patient' below.)

The time course of the clinical response to therapy is illustrated by the following observations:

  • In a prospective, multicenter cohort study of 686 adults hospitalized with CAP, the median time to becoming afebrile, defined as 38.3 ºC (101 ºF), was two days, and three days if defined as either 37.8 ºC (100 ºF) or 37.2 ºC (99 ºF) [57]. However, fever in patients with lobar pneumonia may take three days or longer to improve.
  • In a second prospective, multicenter trial of 1424 patients hospitalized with CAP, the median time to stability (defined as resolution of fever, heart rate <100 beats/min, respiratory rate <24 breaths/min, systolic blood pressure of ≥90 mmHg, and oxygen saturation ≥90 percent for patients not receiving prior home oxygen) was four days [58].

Although a clinical response to appropriate antibiotic therapy is seen relatively quickly, the time to resolution of all symptoms and radiographic findings is more prolonged. With pneumococcal pneumonia, for example, the cough usually resolves within eight days and auscultatory crackles clear within three weeks. (See "Pneumococcal pneumonia in adults".)

In addition, as many as 87 percent of inpatients with CAP have persistence of at least one pneumonia-related symptom (eg, fatigue, cough with or without sputum production, dyspnea, chest pain) at 30 days compared to 65 percent by history in the month prior to the onset of CAP [59]. Patients should be told that some symptoms can last this long so that they are able to set reasonable expectations for their clinical course. (See "Prognosis of community-acquired pneumonia in adults", section on 'Mortality and symptom resolution'.)

Radiographic response — Radiographic improvement typically lags behind the clinical response [60-63]. This issue was addressed in a prospective multicenter trial of 288 patients hospitalized for severe CAP; the patients were followed for 28 days in order to assess the timing of resolution of chest x-ray abnormalities [60]. The following findings were noted:

  • At day 7, 56 percent had clinical improvement but only 25 had resolution of chest x-ray abnormalities.
  • At day 28, 78 percent had attained clinical cure but only 53 percent had resolution of chest x-ray abnormalities. The clinical outcomes were not significantly different between patients with and without deterioration of chest x-ray findings during the follow-up period.
  • Delayed radiographic resolution was independently associated with multilobar disease. In other studies, the timing of radiologic resolution of the pneumonia varied with patient age and the presence of underlying lung disease [61,62]. The chest x-ray usually cleared within four weeks in patients younger than 50 years of age without underlying pulmonary disease. In contrast, resolution could be delayed for 12 weeks or more in older individuals and in those with underlying lung disease.

Switch to oral therapy — Patients requiring hospitalization for CAP are generally begun on intravenous therapy. They can be switched to oral therapy when they are improving clinically, hemodynamically stable, able to take oral medications, and have a normally functioning gastrointestinal tract [2].

Two prospective observational studies in 253 patients evaluated the clinical outcome of an early switch from intravenous to oral therapy in the treatment of CAP [64,65]. Patients met the following criteria prior to switching: resolution of fever, improvement in respiratory function, decrease in white blood cell (WBC) count, and normal gastrointestinal tract absorption. Only two patients failed treatment and the protocol was associated with high patient satisfaction [65].

Similar outcomes were noted in a multicenter randomized trial in the Netherlands of 265 patients with CAP (mean age 70) admitted to non-intensive care wards [66]. Patients were initially treated with three days of intravenous antibiotics and, when clinically stable, were assigned either to oral antibiotics to complete a total course of ten days, or to a standard regimen of seven days of intravenous antibiotics. There was no difference in 28 day mortality (4 versus 2 percent) or clinical cure rate (83 versus 85 percent), while the length of hospital stay was reduced in the oral switch group by a mean of 1.9 days (9.6 versus 11.5 days).

If the pathogen has been identified, the choice of oral antibiotic therapy is based upon the susceptibility profile (table 5). If a pathogen is not identified, the choice of antibiotic for oral therapy is either the same as the intravenous antibiotic, or in the same drug class. In patients who are treated with the combination of intravenous beta-lactam/macrolide, a switch to oral therapy with a macrolide alone is reasonable if there is no risk for DRSP, the prevalence of DRSP is low in the community, and a gram-negative enteric bacillus is not isolated or considered likely based on epidemiologic factors. (See 'Risk factors for drug resistance' above and "Treatment of community-acquired pneumonia in adults in the outpatient setting", section on 'Treatment regimens'.)

Documentation of pneumococcal bacteremia does not appear to alter the effect of switching to oral therapy early (no clinical failures in 18 such patients switched based upon the above criteria in one report) [67].

Duration of hospitalization — Several studies have shown that it is not necessary to observe stable patients overnight after switching from intravenous to oral therapy, although this has been common practice [2,68,69]. As an example, a retrospective review of the United States Medicare National Pneumonia Project database compared outcomes between patients hospitalized for CAP who were not (n = 2536) and were (n = 2712) observed overnight after switching to oral therapy [69]. The following findings were noted:

  • No significant difference in 14-day hospital readmission rate (7.8 versus 7.2 percent)
  • No significant difference in the 30-day mortality rate (5.1 versus 4.4 percent).

The importance of clinical stability at discharge was illustrated in a prospective observational study of 373 Israeli patients discharged with a diagnosis of CAP [70]. On the last day of hospitalization, seven parameters of instability were evaluated (temperature >37.8 ºC [100 ºF], respiratory rate >24/min, heart rate (HR) >100 beats/min, systolic BP ≤90 mmHg, oxygen saturation <90 percent on room air, inability to receive oral nutrition, and change of mental status from baseline). At 60 days post discharge, patients with at least one parameter of instability at discharge were significantly more likely to have died or required readmission than patients with no parameters of instability (death rates, 14.6 versus 2.1 percent; readmission rates, 14.6 versus 6.5 percent).

Duration of therapy — Based upon the available data, we agree with the recommendation of the IDSA/ATS guidelines that patients with CAP should be treated for a minimum of five days [2]. Thus, the recommended duration for patients with good clinical response within the first two to three days of therapy is five to seven days total. Support for this recommendation comes from a meta-analysis of 15 randomized controlled trials of almost 2800 patients with mild to moderate CAP, which found comparable clinical outcomes with less than seven days compared to more than seven days of antimicrobial therapy; however, only two of these trials were specifically about hospitalized patients [71]. (See "Antibiotic studies for the treatment of community-acquired pneumonia in adults", section on 'Duration of therapy'.)

Before stopping therapy, the patient should be afebrile for 48 to 72 hours, breathing without supplemental oxygen (unless required for preexisting disease), and have no more than one clinical instability factor (defined as heart rate [HR] >100 beats/min, respiratory rate [RR] >24 breaths/min, and systolic blood pressure [SBP] ≤90 mmHg) [2].

Longer durations of therapy are needed in the following settings:

  • If the initial therapy was not active against the subsequently identified pathogen (see 'The nonresponding patient' below).
  • If extrapulmonary infection is identified (eg, meningitis or endocarditis).
  • If the patient has pneumonia caused by P. aeruginosa, S. aureus, or Legionella spp, or pneumonia caused by some unusual and less common pathogens (eg, Burkholderia pseudomallei, fungus).
  • If the patient has necrotizing pneumonia, empyema, or lung abscess [72].

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, duration will vary with a recommendation of 7 to 21 days depending upon the extent of infection [25]. In a study of VAP due to MRSA (although not likely due to the USA 300 strain that causes community-acquired MRSA pneumonia), eight days of therapy was as effective as 15 days of therapy [73].

Follow-up chest radiograph — Chest x-ray findings usually clear more slowly than clinical manifestations (see 'Radiographic response' above). Routine chest x-rays for follow-up of CAP patients who are responding clinically are unnecessary. In a large population-based cohort study of patients with CAP, new lung cancer was diagnosed within 90 days of CAP in 1.1 percent and within five years of the index CAP episode in 2.3 percent [74]. On multivariate analysis, the characteristic most strongly associated with lung cancer was an age >50 years (adjusted hazard ratio [HR] 19.0, 95% CI 5.7-63.6); other risk factors were male sex (adjusted HR 1.8, 95% CI 1.1-2.9) and smoking (adjusted HR 1.7, 95% CI 1.0-3.0). Since nearly 99 percent of patients will not have lung cancer after CAP, the authors suggested that routine follow-up chest x-ray is not warranted in patients <50 years of age, except in patients who do not experience a resolution of pneumonia symptoms. This study also indicated that the greatest yield for the diagnosis of cancer would occur if routine follow-up chest x-rays were restricted to patients >50 years of age.

Among patients who have clinical resolution following treatment for CAP, we recommend restricting follow-up chest x-rays to patients >50 years of age; follow-up chest x-ray is particularly important for males and smokers in this age group. When indicated, we suggest that follow-up chest x-rays be performed 7 to 12 weeks following treatment to document resolution of the pneumonia and exclude underlying diseases, such as malignancy [75].

The nonresponding patient — Issues relating to nonresolving pneumonia are discussed in detail separately. This section will be limited to a general overview of nonresponding pneumonia in patients with CAP who require hospitalization. (See "Nonresolving pneumonia".)

Most patients with CAP show clinical improvement within 72 hours of initial antibiotic treatment. It has been estimated that 6 to 15 percent of hospitalized patients with CAP do not respond within this time frame, and the failure rate may be as high as 40 percent in patients initially admitted to an ICU [2,76-78]. These patients have significantly increased mortality compared to responders [2,77,78]. (See "Prognosis of community-acquired pneumonia in adults", section on 'The nonresponding patient'.)

Two general patterns of nonresponse have been described in patients with CAP [2,76]:

  • Progressive pneumonia or clinical deterioration, with requirement for ventilator support and/or septic shock usually occurring in the first 72 hours. Deterioration after 72 hours is often due to an intercurrent complication, progression of the underlying infection, or a superimposed nosocomial infection. Many patients who ultimately require ICU admission for CAP are initially admitted to a non-ICU ward and then transferred because of clinical deterioration (59 of 113 in one report, 50 in the first 24 hours) [79].
  • Persistent or nonresponding pneumonia, defined as the absence of or delay in achieving clinical stability after 72 hours of antibiotic therapy.

The most common causes of treatment failure are lack of or delayed response by the host despite appropriate antibiotics and infection with an organism that is not covered by the initial antibiotic regimen [2,76,80]. Patient-related factors include severity of illness, neoplasia, aspiration pneumonia, and neurologic disease (table 7) [80], while lack of responsiveness to initial therapy may be due to drug-resistant organisms, unusual pathogens (eg, Legionella spp, viruses, fungi including Pneumocystis jirovecii [formerly P. carinii], or Mycobacterium tuberculosis), or an infectious complication, such as postobstructive pneumonia, empyema, abscess, or superimposed nosocomial pneumonia [2,76,81].

In a review of treatment failure in 49 hospitalized patients with CAP, a definite diagnosis was established in 32 and a probable diagnosis was made in nine [76]. The major causes were infection with a pathogen not detected in the initial evaluation (atypical or unusual pathogens or pathogens associated with the development of empyema), persistent infection with the same pathogen, usually reflecting resistance to initial empiric therapy, and nosocomial infection with a new pathogen, most often associated with ventilator-associated pneumonia.

In addition, treatment failure may be wrongly presumed when the infiltrates are responding slowly but the patient has developed a superimposed problem [2,63,76,82]. These include noninfectious entities, such as drug fever, malignancy, interstitial lung disease (eg, bronchiolitis obliterans organizing pneumonia), inflammatory conditions, or heart failure, or a hospital-acquired infection of another body system (eg, intravascular catheter infection, urinary tract infection due to an indwelling urinary catheter, or Clostridium difficile infection) (table 7). Noninfectious causes were considered responsible for nine of the treatment failures in the above series of 49 patients [76].

Treatment failure may also be incorrectly diagnosed in patients who have repeat sputum cultures that grow a new pathogen. The upper airway of hospitalized patients receiving antibiotics may become colonized, particularly with gram-negative bacilli and S. aureus, and may be misinterpreted as contributing to the pneumonia. Thus, repeat sputum cultures should be interpreted with caution.

Risk factors — A number of studies have evaluated risk factors for nonresponse in hospitalized patients with CAP [77,78,83]. The rate of treatment failure in different large series was 13 and 15 percent overall [77,83], with early treatment failure (lack of response or worsening at 48 to 72 hours) occurring in 6 percent [78].

A prospective multicenter study identified risk factors for treatment failure in CAP, which occurred in 15 percent of 1424 hospitalized patients [77]. Independent risk factors were multilobar pneumonia, cavitation on chest x-ray, pleural effusion, liver disease, leukopenia, and a high Pneumonia Severity Index (PSI). Three factors were protective: influenza vaccination, chronic obstructive pulmonary disease, and treatment with a fluoroquinolone.

A second observational analysis of 1383 hospitalized adults with CAP identified the following risk factors for early treatment failure (lack of response or worsening at 48 to 72 hours) [78]:

  • Multilobar pneumonia
  • Pneumonia caused by MRSA, Legionella, or gram-negative bacilli (Enterobacteriaceae or Pseudomonas aeruginosa)
  • PSI >90
  • Treatment with an antimicrobial agent to which the causative organism was not susceptible

Further evaluation — When evaluating a patient who is not responding to therapy, the initial approach may include repeating the history (including travel and pet exposures to look for unusual pathogens), chest x-ray, and sputum and blood cultures [2,76]. If this is unrevealing, then further diagnostic procedures, such as chest CT, bronchoscopy, and, lung biopsy can be performed. (See "Nonresolving pneumonia", section on 'Further evaluation of nonresolving pneumonia'.)

  • Chest CT can detect pleural effusion, lung abscess, or central airway obstruction, all of which can cause treatment failure. It may also detect noninfectious causes such as bronchiolitis obliterans organizing pneumonia [2]. Since empyema and parapneumonic effusion can contribute to nonresponse, thoracentesis should be performed in all nonresponding patients with significant pleural fluid accumulation.
  • Bronchoscopy can evaluate the airway for obstruction due to a foreign body or malignancy, which can cause a postobstructive pneumonia. Protected brushings and bronchoalveolar lavage (BAL) may be obtained for microbiologic and cytologic studies; in some cases, transbronchial biopsy may be helpful. The microbiologic evaluation of the nonresponding patient can be complicated by the effect of the initial antimicrobial therapy that may reduce the yield of pathogen isolation, or select for colonization with resistant organisms. In addition, BAL may reveal evidence of noninfectious disorders or, if there is a lymphocytic rather than neutrophilic alveolitis, viral or Chlamydophila infection [84].

Thoracoscopic or open lung biopsy may be performed if all of these procedures are nondiagnostic and the patient continues to be ill. The advent of thoracoscopic procedures has significantly reduced the need for open lung biopsy, and its associated morbidity.

Management — Failure to respond to antibiotics usually results in one or more of the following: patient transfer to a higher level of care, further diagnostic testing, and/or escalation of or change in treatment [2]. There is no convincing evidence of benefit from combination antibiotic therapy in patients with progressive disease [2] with the exception of those with severe bacteremic pneumococcal pneumonia requiring admission to an ICU; in such patients, the most commonly used combination regimens were a beta-lactam plus a macrolide or vancomycin plus a macrolide [85]. This is a presumed reflection of the primary importance of severe illness at presentation or delayed treatment response due to host factors. (See "Nonresolving pneumonia" and "Pneumococcal pneumonia in adults", section on 'Bacteremic pneumonia'.)

Risk factors for rehospitalization — Risk factors for rehospitalization were assessed in a multicenter randomized trial of hospitalized patients with CAP [86]. Among 577 patients, 70 (12 percent) were rehospitalized within 30 days: 52 were related to comorbidities (most commonly cardiovascular, pulmonary, or neurologic); and 14 were related to pneumonia. Factors that were independently associated with rehospitalization included less than a high school education, unemployment, coronary artery disease, and chronic obstructive pulmonary disease.

In a similar study of 1117 patients from a single center, 81 (7 percent) were rehospitalized within 30 days; 29 due to pneumonia-related causes and the remainder due to pneumonia-unrelated causes [87]. Risk factors for pneumonia-related rehospitalization were initial treatment failure and one or more instability factors (eg, vital signs or oxygenation) on discharge; risk factors for non-pneumonia related readmissions were age ≥65 and decompensated comorbidities (most commonly cardiac or pulmonary).

Adjunctive therapies

Glucocorticoids — There has been interest in using glucocorticoids as adjunctive therapy to antibiotics in hospitalized patients with CAP. However, there are conflicting data on the potential benefit of this approach:

  • A small randomized trial of 46 patients and a retrospective study of 308 patients, 70 of whom received glucocorticoids suggested improvement in survival among patients with severe CAP [88,89].
  • In contrast, a much larger randomized trial of 213 immunocompetent patients did not demonstrate improved outcomes (clinical cure or mortality) in hospitalized patients [90]. Most of these patients did not have severe CAP, but there was also no benefit in the subset of patients with severe disease. In addition, the patients who received glucocorticoids had a higher rate of late failure, which was defined as a recurrence of signs and symptoms of pneumonia >72 hours after admission; this may have been due at least in part to abrupt discontinuation of glucocorticoids, leading to a rebound inflammatory response.
  • A third randomized trial included 304 immunocompetent patients with CAP who were admitted to the hospital but did not require immediate ICU admission; almost one-half had more severe disease as defined by a Pneumonia Severity Index class of IV or V (table 8) [91]. The patients who received glucocorticoids had a significantly shorter median length of hospital stay of one day (6.5 versus 7.5 days). In-hospital mortality was infrequent and not different between the two groups.

The above data do not provide convincing evidence of benefit from glucocorticoid therapy. Whether or not there is a benefit of glucocorticoids in severe CAP is being evaluated in a large Veteran Administration cooperative study, which is investigating prolonged low-dose methylprednisolone treatment in patients admitted to the ICU [92]. Pending these results and based upon the available data, glucocorticoids are not recommended as adjunctive therapy for CAP.

Tissue factor pathway inhibitor — A recombinant tissue factor pathway inhibitor, tifacogin, which is a systemic inhibitor of coagulation, has been evaluated in an international multicenter randomized trial of patients with severe CAP [93]. Despite evidence of biologic activity, tifacogin was not associated with a mortality benefit compared with placebo. Therefore, tifacogin is not recommended in patients with severe CAP.

VACCINATION — Patients with community-acquired pneumonia (CAP) should be appropriately vaccinated for influenza and pneumococcal infection [2]. Screening for influenza vaccination status is warranted during influenza season (eg, from October through March in the northern hemisphere) in all patients. Screening for pneumococcal vaccination status is warranted in patients age 65 or older or with other indications for vaccination (table 9). Vaccination can be administered at any time during hospitalization after the patient has become afebrile.  (See "Seasonal influenza vaccination in adults" and "Pneumococcal vaccination in adults".)

SMOKING CESSATION — Smoking cessation should be a goal for hospitalized patients with community-acquired pneumonia (CAP) who smoke [2]. (See "Overview of smoking cessation management in adults".)

PERFORMANCE MEASURES — The Centers for Medicare and Medicaid Services (CMS), as part of the National Pneumonia Medicare Quality Improvement Project [52] and Joint Commission on Accreditation of Healthcare Organizations (JCAHO), have established performance indicators to assess the quality of hospital care for pneumonia patients. These indicators are also endorsed by the National Quality Forum [52].

The performance measures include:

  • Pneumococcal vaccination
  • Blood cultures
  • Antibiotic administration within six hours of presentation
  • Use of a guideline-compliant antibiotic regimen
  • Influenza vaccination
  • One-step inpatient smoking cessation counseling

The primary intent of these indicators is to implement evidence-based processes of care to maximize survival rates for pneumonia patients. Meta-analysis of each performance measure has shown that the estimated effects favor the interventions recommended for the first five of these measures, although only influenza vaccination is supported by high quality evidence [94].

As of January 2012, several of the CMS performance measures will change [95]. The initial antibiotic timing measure will be retired. Both of the vaccine measures will also be retired as a specific pneumonia measure and become a global measure. Similarly, the smoking cessation measure is pending change as a global measure. .

Compliance with these measures has been linked to reimbursement (ie, Pay for Performance). Concern has been raised that this may drive pressure for hospitals and physicians to act based on these measures rather than on what may be best for an individual patient [96], or for triaging other patients in an emergency department [54]. Specific performance measures cannot cover all host and epidemiologic settings, especially when the presentation of pneumonia is atypical [97], and deviation from the performance measurement criteria may be reasonable in particular circumstances [53]; the reason for deviation should be documented in the chart. A major concern is the need to give antibiotics within six hours has led to antibiotic abuse due to confusion in distinguishing community-acquired pneumonia (CAP) from pulmonary embolism, congestive heart failure, etc. This dilemma has been solved by Medicare by allowing “diagnostic uncertainty” as a valid justification for an antibiotic delay.

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SUMMARY AND RECOMMENDATIONS

  • 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 (table 1 and table 2 and figure 1). The predominant pathogen is Streptococcus pneumoniae. Other common pathogens include Haemophilus influenzae, the atypical bacteria (Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella spp), oropharyngeal aerobes and anaerobes (in the setting of aspiration), and respiratory viruses. (See 'Principles of antimicrobial therapy' above.)
  • 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. (See 'Risk factors for drug resistance' above.)
  • 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, moxifloxacin, or gemifloxacin) (Grade 1B). We suggest monotherapy with tigecycline for patients intolerant of beta-lactams (Grade 2B). Coverage for drug-resistant pathogens, such as Pseudomonas or methicillin-resistant Staphylococcus aureus (MRSA), should be included in patients with risk factors. Doxycycline may be used as an alternative to a macrolide. Oral therapy with a macrolide or doxycycline is appropriate only for selected patients without evidence of or risk factors for severe pneumonia. (See 'Not in the ICU' above.)
  • For hospitalized patients requiring ICU care, we suggest initial combination therapy with an anti-pneumococcal beta-lactam (ceftriaxone, cefotaxime, or ampicillin-sulbactam) plus either intravenous therapy with azithromycin or a respiratory fluoroquinolone (levofloxacin or moxifloxacin) plus vancomycin (15 mg/kg IV every 12 hours, adjusted for a trough level of 15 to 20 mcg/mL and for renal function) or linezolid (600 mg IV twice daily) (Grade 2B). Coverage for other drug-resistant pathogens, such as Pseudomonas, should be included in patients with risk factors. (See 'Admitted to an ICU' above.)
  • We suggest that empiric treatment regimens be modified when results of diagnostic studies indicate a specific pathogen, and coinfection is unlikely based upon clinical or epidemiological 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 x-ray findings usually clear within four weeks but may persist for 12 weeks in older individuals, and those with underlying pulmonary disease. (See 'Clinical response to therapy' above.)
  • 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). (See 'Switch to oral therapy' above.)
  • We suggest hospital discharge when the patient can take oral medication; we suggest not keeping the patient overnight for observation following the switch (Grade 2B). (See 'Duration of hospitalization' above.)
  • 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. (See 'Duration of therapy' above.)
  • Routine follow-up chest x-rays for patients who are responding clinically within the first week are unnecessary. We suggest a follow-up chest x-ray 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 x-ray is particularly important for males and smokers in this age group. (See 'Follow-up chest radiograph' above.)
  • 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 (>90), antibiotic-resistant pathogen, cavitation, pleural effusion, liver disease, and leukopenia. (See 'The nonresponding patient' above.)

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