さまよう薬剤師のブログ

学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist.

[復習]市中肺炎

消化器医師から成人の外来における市中肺炎治療のご相談をいただきました。

A-DROP、PSI、CURB65は低スコア

抗菌薬内服開始72時間においても、臨床的増悪があり非定型を医師と疑い

マクロライド高用量を選択となりました。

医師の優しさで整腸剤も追加となりましたが、毎回必要性を考えてしまいます。

 

以下、復習です。

 

肺炎は難しいと感じています。定義もなんだか曖昧。

抗菌薬開発前と現在の予後に変化がないなど、良くお話を聞きます。

また、近年は肺炎を老衰と捉える考え方も徐々に浸透してきました。

 

Up To Date (本日) より

Treatment of community-acquired pneumonia in adults in the outpatient setting

 

Most initial treatment regimens for community-acquired pneumonia (CAP) are empiric. A limited number of pathogens are responsible for the majority of cases of CAP. Antibiotics should be started as soon as possible once the diagnosis of CAP is established. The presence of an infiltrate on plain chest radiograph is considered the gold standard for diagnosing pneumonia when clinical (and, in some cases, microbiologic) features are supportive.

 

Emerging drug-resistant Streptococcus pneumoniae (DRSP) complicates the use of empiric treatment. Treatment failures have been demonstrated with use of macrolides for macrolide-resistant organisms. We recommend not using macrolide monotherapy for patients who have received an antibiotic within the preceding three months, if the local rate of macrolide resistance is >25 percent (including all regions in the United States and certain other countries) . 

 

Despite in vitro resistance, penicillin-resistant pneumococci may respond to higher-dose beta-lactams other than cefuroxime.

 

North American and British guidelines differ in their recommendations for first-line therapy for outpatient pneumonia. British guidelines promote amoxicillin and place less significance on atypical pathogens. North American guidelines from 2007 advocate treating both atypical pathogens and pneumococcus and suggest macrolides or doxycycline when antibiotic resistance is not anticipated. 

 

For nonhospitalized patients with an established diagnosis of CAP who also have comorbidities, a history of recent antibiotic use, or when the local rate of macrolide resistance is >25 percent (including all regions of the United States and certain other countries), we suggest empiric monotherapy with a respiratory fluoroquinolone or combination therapy with a beta-lactam plus either a macrolide or doxycycline (Grade 2A). Appropriate fluoroquinolones include levofloxacin 750 mg daily, moxifloxacin 400 mg daily, and gemifloxacin 320 mg daily. For nonpregnant patients at risk for QT interval prolongation, we favor combination therapy with a beta-lactam plus doxycycline in order to avoid the QT interval-prolonging effects of fluoroquinolones and macrolides.

 

For uncomplicated pneumonia in patients who have no significant comorbidities and/or risk factors for macrolide resistance (use of antibiotics within the last three months, local rate of macrolide resistance >25 percent), we suggest empiric treatment with an advanced macrolide. Regimens include azithromycin (500 mg on day one followed by four days of 250 mg a day or 500 mg daily for three days), clarithromycin (500 mg twice daily), or clarithromycin XL (two 500 mg tablets once daily). We suggest doxycycline (100 mg twice daily) as an alternative to a macrolide, especially in nonpregnant patients at high risk for QT interval prolongation


Most outpatients with CAP should be treated for five days. Because of its long half-life, patients receiving azithromycin at a dose of 500 mg daily can usually be treated for three days. Therapy should not be stopped until the patient is afebrile for 48 to 72 hours and is clinically stable. When this is achieved, the persistence of other symptoms (eg, dyspnea, cough) is not an indication to extend the course of antibiotic therapy.

 

Patients who have not responded to therapy after 48 to 72 hours should be reevaluated

 

Microbial etiology of community-acquired pneumonia by site of care*
  Outpatients Ward patients Intensive care unit patients
Marrie, et al[1]  Cilllóniz, et al[2]  Cilllóniz, et al[2]  Restrepo, et al[3]  Cilllóniz, et al[2]  Restrepo, et al[3] 
Total patients evaluated 507 514 2521 585 488 145
Patients in whom a pathogen was identified 244 (48.1) 161 (31.3) 1042 (41) 120 (21) 260 (53) 57 (39)
Patients in whom no pathogen was identified 263 (51.9) 353 (68.7) 1479 (59) 465 (79) 228 (47) 88 (61)
Pathogen
Streptococcus pneumoniae 30 (5.9) 56 (10.9) 447 (17.7) 38 (6.5) 110 (22.5) 22 (15.2)
Other Streptococcus spp 5 (1.0) 0 0 0 0 0
Haemophilus influenzae 25 (4.9) 8 (1.6) 54 (2.1) 16 (2.7) 8 (1.6) 3 (2.1)
Haemophilus parainfluenzae 10 (2.0) 0 0 0 0 0
Moraxella cattarrhalis 6 (1.2) 0 4 (0.2) 0 1 (0.2) 0
Legionella pneumophila Δ 10 (1.9) 87 (3.5) 21 (4.3)
Mycoplasma pneumoniae 87 (17.2)§ 27 (5.3)§ 32 (1.3)§ ¥ 6 (1.2)§ ¥
Chlamydophila pneumoniae 72 (14.2)§ 10 (1.9)§ 32 (1.3)§ ¥ 8 (1.6)§ ¥
Coxiella burnetii Δ 11 (2.1)§ 17 (0.7)§ ¥ 2 (0.4)§ ¥
Staphylococcus aureus 6 (1.2) 1 (0.2) 18 (0.7) 25 (4.3) 6 (1.2) 12 (8.3)
MSSA NR 1 (0.2) 9 (0.4) 18 (3.1) 4 (0.8) 9 (6.2)
MRSA NR 0 9 (0.4) 7 (1.2) 2 (0.4) 3 (2.1)
Gram-negative enteric bacilli 2 (0.4) 1 (0.2) 23 (0.9) 15 (2.6) 3 (0.6) 4 (2.8)
Pseudomonas aeruginosa 1 (0.2) 1 (0.2) 37 (1.5) 12 (2.1) 12 (2.5) 8 (5.5)
Respiratory viruses 15 (2.9)§ 123 (4.9)§ 10 (2.0)§
Other pathogen 14 (2.8) 6 (1.2) 33 (1.3) 8 (1.4) 15 (3.1) 3 (2.1)
>1 pathogen ** 15 (2.9) 135 (5.4) 6 (1.0) 58 (11.9) 7 (4.8)
Diagnostic methods Cultures (sputum, blood), serologic testing (for M. pneumoniaeC. pneumoniae) Cultures (sputum, blood, transthoracic needle aspirate, transbronchial aspirates, bronchoalveolar lavage [BAL] fluid, protected specimen brush respiratory samples, pleural fluid), serologic testing (for M. pneumoniaeC. pneumoniaeL. pneumophilaC. burnetti, influenza A and B, parainfluenza viruses 1-3, respiratory syncytial virus, adenovirus), urinary antigen testing (for S. pneumoniae and L. pneumophila), immunofluorescence assay plus virus isolation or reverse transcriptase polymerase chain reaction [PCR] for influenza A and B, parainfluenza viruses 1-3, respiratory syncytial virus, adenovirus Cultures (sputum, blood, transthoracic needle aspirate, transbronchial aspirates, BAL fluid, protected specimen brush respiratory samples, pleural fluid), serologic testing (for M. pneumoniaeC. pneumoniaeL. pneumophilaC. burnetti, influenza A and B, parainfluenza viruses 1-3, respiratory syncytial virus, adenovirus), urinary antigen testing (for S. pneumoniae and L. pneumophila), immunofluorescence assay plus virus isolation or reverse transcriptase polymerase chain reaction [PCR] for influenza A and B, parainfluenza viruses 1-3, respiratory syncytial virus, adenovirus Cultures (blood, endotracheal aspirates, protected specimen brush respiratory samples, BAL fluid, pleural fluid), urinary antigen (for L. pneumophila) Cultures (sputum, blood, transthoracic needle aspirate, transbronchial aspirates, BAL fluid, protected specimen brush respiratory samples, pleural fluid), serologic testing (for M. pneumoniaeC. pneumoniaeL. pneumophilaC. burnetti, influenza A and B, parainfluenza viruses 1-3, respiratory syncytial virus, adenovirus), urinary antigen testing (for S. pneumoniae and L. pneumophila), immunofluorescence assay plus virus isolation or reverse transcriptase polymerase chain reaction [PCR] for influenza A and B, parainfluenza viruses 1-3, respiratory syncytial virus, adenovirus Cultures (blood, endotracheal aspirates, protected specimen brush respiratory samples, BAL fluid, pleural fluid), urinary antigen testing (for L. pneumophila)
MSSA: methicillin-susceptible Staphylococcus aureus; MRSA: methicillin-resistant Staphylococcus aureus; NR: not reported.
* Results are reported as number of patients (percent). Different methods were used for diagnosis in each study, as described in the row on diagnostic methods.
 Results are reported as the number of patients with a given pathogen, followed by the percentage of patients in whom the pathogen was identified out of all of the patients in the study. For example, in the first column, S. pneumoniae was detected in 30 of 507 patients in the study (5.9 percent). Among the 244 patients in whom a pathogen was identified, S. pneumoniae was detected in 12.3 percent.
Δ Testing for Legionella spp and C. burnetti was not performed.
 Legionella urinary antigen testing was performed in 35 ward patients and 26 intensive care unit patients, but all results were negative. Legionella culture was not performed.
§ Pathogens detected by serologic methods may represent recent infection rather than active infection.
¥ Testing for M. pneumoniaeC. pneumoniae, and C. burnetii was not performed.
‡ Influenza viruses A or B, parainfluenza viruses 1-3, respiratory syncytial virus, adenovirus.
† Testing for viruses was not performed.
** Some patients had >1 pathogen isolated, but the details were not reported.
References:
  1. Marrie TJ, Poulin-Costello M, Beecroft MD, Herman-Bnjidic Z. Etiology of community-acquired pneumonia treated in an ambulatory setting. Resp Medicine 2005; 99:60.
  2. Cillóniz C, Ewig S, Polverino E, et al. Microbial aetiology of community-acquired pneumonia and its relation to severity. Thorax 2011; 66:340.
  3. Restrepo MI, Mortensen EM, Velez JA, et al. A comparative study of community-acquired pneumonia patients admitted to the ward and the ICU. Chest 2008; 133:610.
Graphic 72014 Version 6.0
 
IDSA/ATS guidelines: Recommended empiric antibiotics for community-acquired pneumonia in adults
Outpatient treatment
1. Previously healthy and no use of antimicrobials within the previous three months:

A macrolide (azithromycin, clarithromycin, or erythromycin)

OR

Doxycyline*

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; or use of antimicrobials within the previous three months (in which case an alternative from a different class should be selected):

A respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin [750 mg])

OR

A beta-lactam (first-line agents: high-dose amoxicillin, amoxicillin-clavulanate; alternative agents: ceftriaxone, cefpodoxime, or cefuroxime) PLUS a macrolide (azithromycin, clarithromycin, or erythromycin)*

3. In regions with a high rate (>25 percent) of infection with high-level (MIC ≥16 mcg/mL) macrolide-resistant Streptococcus pneumoniae, consider use of alternative agents listed in (2) above.
Inpatients, non-ICU treatment

A respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin [750 mg])

OR

An antipneumococcal beta-lactam (preferred agents: cefotaxime, ceftriaxone, or ampicillin-sulbactam; or ertapenem for selected patients) PLUS a macrolide (azithromycin, clarithromycin, or erythromycin)*Δ

Inpatients, ICU treatment

An antipneumococcal beta-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) PLUS azithromycin

OR

An antipneumococcal beta-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) PLUS a respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin [750 mg])

OR

For penicillin-allergic patients, a respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin [750 mg]) PLUS aztreonam

Special concerns
If Pseudomonas aeruginosa is a consideration:

An antipneumococcal, antipseudomonal beta-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) PLUS either ciprofloxacin or levofloxacin (750 mg)

OR

The above beta-lactam PLUS an aminoglycoside PLUS azithromycin

OR

The above beta-lactam PLUS an aminoglycoside PLUS a respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin [750 mg]); for penicillin-allergic patients, substitute aztreonam for above beta-lactam

If CA-MRSA is a consideration:
Add vancomycin or linezolid
This table provides the 2007 recommendations of the Infectious Diseases Society of America and the American Thoracic Society (IDSA/ATS) for reference purposes. Please see the UpToDate text for information about choosing between the different guidelines and about the preferred doses and durations of the individual antibiotics.
CAP: community-acquired pneumonia; CA-MRSA: community-acquired methicillin-resistant Staphylococcus aureus; ICU: intensive care unit; MIC: minimum inhibitory concentration.
* Doxycycline may be used as an alternative to a macrolide, but there is stronger evidence to support the use of a macrolide than doxycycline for CAP.
 Ceftaroline can be used as an alternative to these agents. It is a fifth-generation cephalosporin that was not included in the 2007 IDSA/ATS guidelines for the management of CAP since it was not US Food and Drug Administration (FDA)-approved for CAP until 2010. Ceftaroline has a spectrum of activity like that of ceftriaxone, including good in vivo activity againstStreptococcus pneumoniae. It is also active against methicillin-resistant Staphylococcus aureus (MRSA), unlike older cephalosporins. However, it is not FDA-approved for CAP involving MRSA since patients with MRSA were excluded from the trials. Ceftaroline is more expensive (average wholesale price 82 USD per day) compared with the alternative agents, which are all off patent. (File TM Jr, Low DE, Eckburg PB, et al. Integrated analysis of FOCUS 1 and FOCUS 2: randomized, doubled-blinded, multicenter phase 3 trials of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in patients with community-acquired pneumonia. Clin Infect Dis 2010; 51:1395.)
Δ Monotherapy with tigecycline may be used in patients who cannot take either a beta-lactam or a fluoroquinolone. Tigecycline was not included in the 2007 IDSA/ATS guidelines for the management of CAP because it was not FDA-approved for CAP until 2009. It has been associated with increased mortality, as discussed further in the topic review.
Modified with permission from: Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27. Copyright © 2007 University of Chicago Press.
Graphic 71665 Version 13.0
 
British Thoracic Society guidelines: Initial empirical treatment regimens for community-acquired pneumonia (CAP) in adults
Pneumonia severity (based on clinical judgement supported by CURB65 severity score) Treatment site Preferred treatment Alternative treatment
Low severity (eg, CURB65 = 0 to 1 or CRB65 score = 0, <3 percent mortality) Home Amoxicillin 500 mg orally three times daily Doxycycline 200 mg loading dose then 100 mg orally once daily or clarithromycin 500 mg orally twice daily
Low severity (eg, CURB65 = 0 to 1, <3 percent mortality) but admission indicated for reasons other than pneumonia severity (eg, social reasons/unstable comorbid illness) Hospital

Amoxicillin 500 mg orally three times daily

If oral administration not possible: amoxicillin 500 mg IV three times daily*
Doxycycline 200 mg loading dose then 100 mg orally once daily or clarithromycin 500 mg orally twice daily
Moderate severity (eg, CURB65 = 2, 9 percent mortality) Hospital

Amoxicillin 500 mg to 1 gram orally three times daily plus clarithromycin 500 mg orally twice daily

If oral administration not possible: amoxicillin 500 mg IV three times daily* or benzylpenicillin (penicillin G) 1.2 grams IV four times daily plusclarithromycin 500 mg IV twice daily*
Doxycycline 200 mg loading dose then 100 mg orally or levofloxacin 500 mg orally once daily ormoxifloxacin 400 mg orally once daily
High severity (eg, CURB65 = 3 to 5, 15 to 40 percent mortality) Hospital (consider critical care review)

Antibiotics given as soon as possible

Co-amoxiclav (amoxicillin-clavulanate potassium) 1.2 grams IV three times daily* plus clarithromycin 500 mg IV twice daily*

(If Legionella strongly suspected, consider adding levofloxacinΔ)

Benzylpenicillin (penicillin G) 1.2 grams IV four times daily plus either levofloxacin 500 mg IV twice dailyor ciprofloxacin 400 mg IV twice daily

OR

Cefuroxime 1.5 grams IV three times daily orcefotaxime 1 gram IV three times daily orceftriaxone 2 grams IV once daily, plusclarithromycin 500 mg IV twice daily*

(If Legionella strongly suspected, consider adding levofloxacinΔ)
This table provides the 2009 guideline recommendations of the British Thoracic Society (BTS) for reference purposes. Please see the UpToDate text for information about choosing between the different guidelines and about the preferred doses and durations of the individual antibiotics.
IV: intravenous.
* Intravenous preparation not available in the United States.
 Following reports of an increased risk of adverse hepatic reactions associated with oral moxifloxacin, in October 2008 the European Medicines Agency (EMEA) recommended that moxifloxacin "should be used only when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of this infection".
Δ Caution: Risk of QT prolongation with macrolide-quinolone combination.
Reproduced with permission from: Lim WS, Baudouin SV, George RC, et al. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax 2009; 64 Suppl 3:iii1. Copyright © 2009 BMJ Publishing Group Ltd.
Graphic 74382 Version 9.0

 

Usual duration of findings in treated community-acquired pneumonia
Abnormality Duration (days)
Tachycardia and hypotension 2
Fever, tachypnea, and hypoxia 3
Cough 14
Fatigue 14
Infiltrates on chest radiograph 30
References:
  1. Marrie TJ, Beecroft MD, Herman-Gnjidic Z. Resolution of symptoms in patients with community-acquired pneumonia treated on an ambulatory basis. J Infect 2004; 49:302.
  2. Metlay JP, Atlas SJ, Borowsky LH, Singer DE. Time course of symptom resolution in patients with community-acquired pneumonia. Respir Med 1998; 92:1137.
  3. Fine MJ, Stone RA, Singer DE, et al. Processes and outcomes of care for patients with community-acquired pneumonia: results from the Pneumonia Patient Outcomes Research Team (PORT) cohort study. Arch Intern Med 1999; 159:970.
Graphic 74599 Version 2.0
 
 
私の市中肺炎の考え方は、
医師と重症度を慎重に捉える。
キノロン以外から考える。(結核マスクを経験しました!

この2点を大切にしています。