Implementation of Guideline Recommendations

  1. Locally adapted guidelines should be implemented to improve process of care variables and relevant clinical outcomes. (Strong recommendation; level I evidence) 很重要的一點 治療肺炎的guideline應該因地制宜

Documented Benefits

  1. Community acquired pneumonia (CAP) guidelines should address a comprehensive set of elements in the process of care rather than a single element in isolation. (Strong recommendation; level III evidence)
  2. Development of local CAP guidelines should be directed toward improvement in specific and clinically relevant outcomes. (Moderate recommendation; level III evidence)

    See Table 3 in the original guideline document for a list of clinically relevant outcome parameters in community acquired pneumonia.

Site-of-Care Decisions

Hospital Admission Decision

  1. Severity-of-illness scores, such as the CURB-65 criteria (confusion, uremia, respiratory rate, low blood pressure, age 65 years or greater), or prognostic models, such as the Pneumonia Severity Index (PSI), can be used to identify patients with CAP who may be candidates for outpatient treatment. (Strong recommendation; level I evidence)

重要 切記!!!當病人有意識不清 BUN>20,呼吸速率>30/min,SBP<90mmHg,Age>65-->CURB-65 score

  1. Objective criteria or scores should always be supplemented with physician determination of subjective factors, including the ability to safely and reliably take oral medication and the availability of outpatient support resources. (Strong recommendation; level II evidence)
  2. For patients with CURB-65 scores >2, more-intensive treatment—that is, hospitalization or, where appropriate and available, intensive in-home health care services—is usually warranted. (Moderate recommendation; level III evidence)

Intensive Care Unit (ICU) Admission Decision

  1. Direct admission to an ICU is required for patients with septic shock requiring vasopressors or with acute respiratory failure requiring intubation and mechanical ventilation. (Strong recommendation; level II evidence) 當病人有敗血性休克 呼吸衰竭需要插管 基本上就需住到ICU
  2. 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 the Table below. (Moderate recommendation; level II evidence)
Table. Criteria for Severe Community-acquired Pneumonia
Minor criteriaa
  • Respiratory rateb >30 breaths/min
  • PaO2/FiO2 ratiob <250
  • Multilobar infiltrates
  • Confusion/disorientation
  • Uremia (BUN level, >20 mg/dL)
  • Leukopeniac (WBC count, <4000 cells/mm3)
  • Thrombocytopenia (platelet count, < 100,000 cells/mm3)
  • Hypothermia (core temperature, <36 degrees C)
  • Hypotension requiring aggressive fluid resuscitation
Major criteria
  • Invasive mechanical ventilation
  • Septic shock with the need for vasopressors

NOTE. BUN, blood urea nitrogen; PaO2/FiO2, arterial oxygen pressure/fraction of inspired oxygen; WBC, white blood cell.
a Other criteria to consider include hypoglycemia (in nondiabetic patients), acute alcoholism/alcoholic withdrawal, hyponatremia, unexplained metabolic  acidosis or elevated lactate level, cirrhosis, and asplenia.
b A need for noninvasive ventilation can substitute for a respiratory rate >30 breaths/min or a PaO2/FiO2 ratio <250.
c As a result of infection alone.

Diagnostic Testing

  1. In addition to a constellation of suggestive clinical features, a demonstrable infiltrate by chest radiograph or other imaging technique, with or without supporting microbiological data, is required for the diagnosis of pneumonia. (Moderate recommendation: level III evidence)

Recommended Diagnostic Tests for Etiology

  1. Patients with CAP should be investigated for specific pathogens that would significantly alter standard (empirical) management decisions, when the presence of such pathogens is suspected on the basis of clinical and epidemiologic clues. (Strong recommendation; level II evidence)
  2. Routine diagnostic tests to identify an etiologic diagnosis are optional for outpatients with CAP. (Moderate recommendation; level III evidence)
  3. Pretreatment blood samples for culture and an expectorated sputum sample for stain and culture (in patients with a productive cough) should be obtained from hospitalized patients with the clinical indications listed in the Table below, but are optional for patients without these conditions. (Moderate recommendation; level I evidence) S/C,blood culture,Gram stain都可以提供我們治療的方向
  4. Pretreatment Gram stain and culture of expectorated sputum should be performed only if a good-quality specimen can be obtained and quality performance measures for collection, transport, and processing of samples can be met. (Moderate recommendation; level II evidence)
  5. Patients with severe CAP, as defined in the guideline should at least have blood samples drawn for culture, urinary antigen tests for Legionella pneumophila and Streptococcus pneumoniae performed, and expectorated sputum samples collected for culture. For intubated patients, an endotracheal aspirate sample should be obtained. (Moderate recommendation; level II evidence)

ICU的病人最好多survey Legionella and pneumococcal urinary antigen

Table. Clinical Indications for More Extensive Diagnostic Testing
IndicationBlood CultureSputum CultureLegionella UATPneumococcal UATOther
Intensive care unit admission X X X X Xa
Failure of outpatient antibiotic therapy   X X X  
Cavitary infiltrates X X     Xb
Leukopenia X     X  
Active alcohol abuse X X X X  
Chronic severe liver disease X     X  
Severe obstructive/ structural lung disease   X      
Asplenia (anatomic or functional) X     X  
Recent travel (within past 2 weeks)     X   Xc
Positive Legionella UAT result   Xd NA    
Positive pneumococcal UAT result X X   NA  
Pleural effusion X X X X Xe

NOTE. NA, not applicable; UAT, urinary antigen test.
a Endotracheal aspirate if intubated, possibly bronchoscopy or nonbronchoscopic bronchoalveolar lavage.
b Fungal and tuberculosis cultures.
c See table 8 in the original guideline document for details.
d Special media for Legionella.
e Thoracentesis and pleural fluid cultures.

Antibiotic Treatment

A major goal of therapy is eradication of the infecting organism, with resultant resolution of clinical disease. As such, antimicrobials are a mainstay of treatment. Appropriate drug selection is dependent on the causative pathogen and its antibiotic susceptibility.

Recommendations are generally for a class of antibiotics rather than a specific drug, unless outcome data clearly favor one drug. Because overall efficacy remains good for many classes of agents, the more potent drugs are given preference because of their benefit in decreasing the risk of selection for antibiotic resistance. Other factors for consideration of specific antimicrobials include pharmacokinetics/pharmacodynamics, compliance, safety, and cost.

Empirical Antimicrobial Therapy

Outpatient Treatment

The following regimens are recommended for outpatient treatment on the basis of the listed clinical risks.

  1. Previously healthy and no risk factors for drug-resistant Streptococcus pneumoniae (DRSP) infection:
    1. A macrolide (azithromycin, clarithromycin, or erythromycin) (Strong recommendation; level I evidence) 如果沒有其他的underlying disease,口服macrolide即可
    2. Doxycycline (Weak recommendation; level III evidence)
  2. Presence of comorbidities, such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancies; asplenia; immunosuppressing conditions or use of immunosuppressing drugs; use of antimicrobials within the previous 3 months (in which case an alternative from a different class should be selected); or other risks for DRSP infection:
    1. A respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin [750 mg]) (Strong recommendation; level I evidence)
    2. A beta-lactam plus a macrolide (Strong recommendation; level I evidence) (High-dose amoxicillin [e.g., 1 g 3 times daily] or amoxicillin-clavulanate [2 g 2 times daily] is preferred; alternatives include ceftriaxone, cefpodoxime, and cefuroxime [500 mg 2 times daily]; doxycycline (level II evidence) is an  alternative to the macrolide.)

                    如果本身有慢性疾病 如DM,alcoholism,asplenia,免疫功能低下,須考慮PRSP,可使用上述兩種選擇

                    

  1. In regions with a high rate (>25%) of infection with high-level (minimal inhibitory concentration [MIC], >16 micrograms/mL) macrolide-resistant S. pneumoniae, consider the use of alternative agents listed above in recommendation 16 for any patient, including those without comorbidities. (Moderate recommendation; level III evidence)

Inpatient, Non-ICU Treatment

The following regimens are recommended for hospital ward treatment.

  1. A respiratory fluoroquinolone (Strong recommendation; level I evidence)
  2. A beta-lactam plus a macrolide (Strong recommendation; level I evidence) (Preferred beta-lactam agents include cefotaxime, ceftriaxone, and ampicillin; ertapenem for selected patients; with doxycycline (level III evidence) as an alternative to the macrolide. A respiratory fluoroquinolone should be used for penicillin-allergic patients.)

Inpatient, ICU Treatment

The following regimen is the minimal recommended treatment for patients admitted to the ICU.

  1. A beta-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus either azithromycin (level II evidence) or a fluoroquinolone (Strong recommendation; level I evidence) (For penicillin-allergic patients, a respiratory fluoroquinolone and aztreonam are recommended.)
  2. For Pseudomonas infection, use an antipneumococcal, antipseudomonal beta-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus either ciprofloxacin or levofloxacin (750-mg dose)

    or

    the above beta-lactam plus an aminoglycoside and azithromycin

    or

    the above beta-lactam plus an aminoglycoside and an antipneumococcal fluoroquinolone (for penicillin-allergic patients, substitute aztreonam for the above beta-lactam). (Moderate recommendation; level III evidence)

          如果是綠膿桿菌感染 可使用抗綠膿桿菌之b-lactam加上ciprofloxacin or levofloxacin

          或是抗綠膿桿菌之b-lactam加上aminoglycoside+azithromycin

          或是抗綠膿桿菌之b-lactam加上aminoglycoside+ciprofloxacin or levofloxacin

  1. For community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection, add vancomycin or linezolid. (Moderate recommendation; level III evidence)

          社區感染之MRSA 加上vancomycin or linezolid

Pathogens Suspected on the Basis of Epidemiologic Considerations

Clinicians should be aware of epidemiologic conditions and/ or risk factors that may suggest that alternative or specific additional antibiotics should be considered. These conditions and specific pathogens, with preferred treatment, are listed in tables 8 and 9 in the original guideline document.

Pathogen-directed Therapy

  1. Once the etiology of CAP has been identified on the basis of reliable microbiological methods, antimicrobial therapy should be directed at that pathogen (Moderate recommendation; level III evidence)
  2. Early treatment (within 48 h of the onset of symptoms) with oseltamivir or zanamivir is recommended for influenza A. (Strong recommendation; level I evidence) A型流感要盡早投藥
  3. Use of oseltamivir and zanamivir is not recommended for patients with uncomplicated influenza with symptoms for >48 h (level I evidence), but these drugs may be used to reduce viral shedding in hospitalized patients or for influenza pneumonia. (Moderate recommendation; level III evidence)

Pandemic Influenza

  1. Patients with an illness compatible with influenza and with known exposure to poultry in areas with previous H5N1 infection should be tested for H5N1 infection. (Moderate recommendation; level III evidence)
  2. In patients with suspected H5N1 infection, droplet precautions and careful routine infection control measures should be used until an H5N1 infection is ruled out. (Moderate recommendation; level III evidence)
  3. Patients with suspected H5N1 infection should be treated with oseltamivir (level II evidence) and antibacterial agents targeting S. pneumoniae and S. aureus, the most common causes of secondary bacterial pneumonia in patients with influenza. (Moderate recommendation; level III evidence)

Time to First Antibiotic Dose

  1. For patients admitted through the emergency department (ED), the first antibiotic dose should be administered while still in the ED. (Moderate recommendation; level III evidence)

Switch from Intravenous to Oral Therapy

  1. Patients should be switched from intravenous to oral therapy when they are hemodynamically stable and improving clinically, are able to ingest medications, and have a normally functioning gastrointestinal tract. (Strong recommendation; level II evidence)
  2. Patients should be discharged as soon as they are clinically stable, have no other active medical problems, and have a safe environment for continued care. Inpatient observation while receiving oral therapy is not necessary. (Moderate recommendation; level II evidence)

Duration of Antibiotic Therapy

  1. Patients with CAP should be treated for a minimum of 5 days (level I evidence), should be afebrile for 48 to 72 h, and should have no more than 1 CAP-associated sign of clinical instability (see Table below) before discontinuation of therapy. (level II evidence) (Moderate recommendation)

          至少治療五天 且有二到三天不燒 另外臨床狀況要穩定!

 

  1. A longer duration of therapy may be needed if initial therapy was not active against the identified pathogen or if it was complicated by extrapulmonary infection, such as meningitis or endocarditis. (Weak recommendation; level III evidence)

Table. Criteria for Clinical Stability重要 記記記!!

  • Temperature <37.8 degrees C
  • Heart rate <100 beats/min
  • Respiratory rate <24 breaths/min
  • Systolic blood pressure >90 mm Hg
  • Arterial oxygen saturation >90% or pO2 >60 mm Hg on room air
  • Ability to maintain oral intake*
  • Normal mental status*

NOTE: Criteria are from (Ramirez et al., 1995; Halm et al., 1998; Menendez et al., 2004). pO2, oxygen partial pressure.
*Important for discharge or oral switch decision but not necessarily for determination of nonresponse.

Other Treatment Considerations

  1. Patients with CAP who have persistent septic shock despite adequate fluid resuscitation should be considered for treatment with drotrecogin alfa activated within 24 h of admission. (Weak recommendation; level II evidence) APC可以在refractory septic shock 病人上考慮使用
  2. Hypotensive, fluid-resuscitated patients with severe CAP should be screened for occult adrenal insufficiency. (Moderate recommendation; level II evidence) 重要 在septic shock病人上常有relative adrenal insufficiency
  3. Patients with hypoxemia or respiratory distress should receive a cautious trial of noninvasive ventilation (NIV) unless they require immediate intubation because of severe hypoxemia (arterial oxygen pressure/fraction of inspired oxygen [PaO2/FiO2] ratio <150) and bilateral alveolar infiltrates. (Moderate recommendation; level I evidence)
  4. Low-tidal-volume ventilation (6 cm3/kg of ideal body weight) should be used for patients undergoing ventilation who have diffuse bilateral pneumonia or acute respiratory distress syndrome. (Strong recommendation; level I evidence)

Management of Nonresponding Pneumonia

Because of the limitations of diagnostic testing, the majority of CAP is still treated empirically. Critical to empirical therapy is an understanding of the management of patients who do not follow the normal response pattern.

Definitions and Classification

The term "nonresponding pneumonia" is used to define a situation in which an inadequate clinical response is present despite antibiotic treatment.

  1. The use of a systematic classification of possible causes of failure to respond, based on time of onset and type of failure (See Table below) is recommended. (Moderate recommendation; level II evidence)
Table. Patterns and Etiologies of Types of Failure to Respond
Failure to improve

Early (<72 h of treatment)

  • Normal response

Delayed

  • Resistant microorganism
    • Uncovered pathogen
    • Inappropriate by sensitivity
  • Parapneumonic effusion/empyema
  • Nosocomial superinfection
    • Nosocomial pneumonia
    • Extrapulmonary
  • Noninfectious
    • Complication of pneumonia (e.g., BOOP)
    • Misdiagnosis: PE, CHF, vasculitis
    • Drug fever
Deterioration or progression

Early (<72 h of treatment)

  • Severity of illness at presentation
  • Resistant microorganism
    • Uncovered pathogen
    • Inappropriate by sensitivity
  • Metastatic infection
    • Empyema/parapneumonic
    • Endocarditis, meningitis, arthritis
  • Inaccurate diagnosis
    • PE, aspiration, ARDS
    • Vasculitis (e.g., SLE)

Delayed

  • Nosocomial superinfection
    • Nosocomial pneumonia
    • Extrapulmonary
  • Exacerbation of comorbid illness
  • Intercurrent noninfectious disease
    • PE
    • Myocardial infarction
    • Renal failure

NOTE. ARDS, acute respiratory distress syndrome; BOOP, bronchiolitis obliterans organizing pneumonia; CHF, congestive heart failure; PE, pulmonary embolus; SLE, systemic lupus erythematosis.

Definitions:

Strength of Recommendation

The strength of each recommendation was graded as "strong," "moderate," or "weak." Each committee member independently graded each recommendation on the basis of not only the evidence but also expert interpretation and clinical applicability. The final grading of each recommendation was a composite of the individual committee members' grades. For the final document, a strong recommendation required >6 (of 12) of the members to consider it to be strong and the majority of the others to grade it as moderate.

The implication of a strong recommendation is that most patients should receive that intervention. While the committee members feel strongly that 100% compliance with guidelines is not the desired goal, the rationale for variation from a strongly recommended guideline should be apparent from the medical record.

Conversely, moderate or weak recommendations suggest that, even if a majority would follow the recommended management, many practitioners may not.

Quality of Evidence

Level I (high): Evidence from well-conducted, randomized controlled trials.

Level II (moderate): Evidence from well-designed, controlled trials without randomization (including cohort, patient series, and case-control studies). Level II studies also include any large case series in which systematic analysis of disease patterns and/or microbial etiology was conducted, as well as reports of data on new therapies that were not collected in a randomized fashion.

Level III (low): Evidence from case studies and expert opinion. In some instances, therapy recommendations come from antibiotic susceptibility data without clinical observations.

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