Pneumonia, Community-Acquired: Treatment & Medication

From: e-medicine

Author: Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University HospitalContributor Information and Disclosures
Updated: Apr 14, 2010
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Overview
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Treatment & Medication
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Therapeutic principles in community-acquired pneumonia

Pathogens
Single pathogens almost always cause community-acquired pneumonia (CAP). Multiple pathogens rarely, if ever, cause CAP.
CAP is almost never caused by more than one typical or two atypical organisms or multiple typical/atypical organisms. Studies that report multiple pathogens are flawed and demonstrate one organism microbiologically with serologic evidence of prior exposure to the other pathogen. Clinical experience has demonstrated this principle for decades.
The only cause of multiple-pathogen pneumonia is aspiration pneumonia.
Comorbid conditions
Comorbid conditions do not affect selection of antimicrobial therapy.
Monotherapy is as effective as multidrug therapy.
The addition and/or change of antibiotics based on severity of illness and/or comorbidities is irrational.
Antimicrobial therapy is directed against the pathogen rather than against the comorbid factors.
Comorbidity is an important prognostic factor and contributes to the severity index but has no place in antibiotic selection.
Severity
The severity of CAP is determined by underlying conditions of the lungs, heart, and spleen.
Do not change antibiotics or use additional antibiotics to treat severe CAP.
Additional antibiotics do not affect the pulmonary, cardiac, or splenic dysfunction that determines clinical severity.
CAP that presents with hypotension and/or shock is due to underlying lung disease, cardiac disease, acute myocardial infarction, or an exacerbation of CHF.
Antibiotic monotherapy is the same for mild, moderate, or severe CAP.
Rapid cavitation is not a typical feature of CAP. CA-MRSA CAP presents as a fulminant CAP with rapid cavitation and necrotizing pneumonia caused by CA-MRSA (SCC mec IV) with the PVL gene, which follows influenza.
Appropriate empiric coverage
In normal hosts, therapy does not need to cover S aureus, Klebsiella species, or P aeruginosa in CAP. (Most CAP regimens include K pneumoniae coverage.) S aureus coverage should be included in patients with influenza who have focal infiltrates.
Most antibiotics used to treat community-acquired aspiration pneumonia (eg, doxycycline, respiratory quinolones, beta-lactams) are highly effective against oral anaerobes. Metronidazole and clindamycin are usually unnecessary. For aerobic lung abscesses, clindamycin or moxifloxacin is preferable.
Coverage should include the typical (S pneumoniae, H influenzae, M catarrhalis) and atypical (Legionella and Mycoplasma species, C pneumoniae) pathogens.
Therapeutic considerations
Monotherapy coverage of both typical and atypical pathogens in CAP is preferred over double-drug therapy.
Monotherapy is less expensive and as effective as double-drug regimens.
Avoid empiric macrolide monotherapy because approximately 25% of S pneumoniae strains are naturally resistant to all macrolides.
Preferred monotherapy for CAP includes doxycycline or a respiratory quinolone.
This is the least expensive way to optimally treat CAP.
No increased resistance is noted with extensive use.
No serious adverse effects are noted.
It is well tolerated in both oral and intravenous forms.
It is ideal for intravenous-to-oral switch monotherapy in terms of patient compliance, safety, and cost.
In patients with CAP who are able to take oral medication, switch from intravenous to oral administration after 48 hours, using an antibiotic with the appropriate spectrum, high bioavailability, minimal adverse gastrointestinal effect profile, little or no resistance potential, and relatively low cost such as doxycycline or a respiratory quinolone.
Most penicillin resistance is relative resistance and is readily treatable with penicillin and/or beta-lactams.
Most highly penicillin-resistant S pneumoniae infections (minimum inhibitory concentration [MIC] >2 µg/mL) may also be treated with beta-lactams. Alternately, doxycycline or respiratory quinolones may be used. Vancomycin is rarely, if ever, needed.
Very highly penicillin-resistant S pneumoniae (MIC 6 µg/mL) strains are a rare cause of CAP but remain susceptible to ceftriaxone.
Treatment measures
Patients with CAP who are moderately to severely ill should be hospitalized. Factors that predict an increased risk of mortality in patients with CAP have been studied and include older age, significant comorbidities, increased respiratory rate, hypotension, fever, multilobar involvement, anemia, and hypoxia, among others.
Patients with severe CAP require admission to an intensive care unit (ICU). Oxygen and/or ventilatory support may be required.
Because the severity of CAP frequently is due to underlying severe cardiopulmonary disease, direct medical efforts at supporting cardiopulmonary function while administering antibiotics for CAP.
Patients admitted with severe CAP and hypotension or shock are often hypotensive because of an acute pulmonary or cardiac insult such as pulmonary embolism or acute myocardial infarction.
If no acute cardiopulmonary explanation can be found (eg, exacerbation of severe underlying lung disease, exacerbation of pre-existing CHF), patients with shock likely have diminished or absent splenic function.
Many underlying conditions are associated with diminished splenic function that may manifest as severe CAP (see Causes).
An abdominal scar due to abdominal trauma or lymphoma staging is a probable sign that the patient has asplenia.
Howell-Jolly bodies in the peripheral blood smear in a patient presenting with CAP who is in shock suggest hyposplenism. The first step in treating a patient in shock is effective intravascular volume replacement. If aggressive intravascular replacement is inadequate, pressors may be added. Do not administer pressors before adequate volume replacement because effective intracirculating intravascular volume will decrease and the blood pressure will drop further.

Treatment of penicillin-resistant pneumococcal pneumonia is as follows:
The overuse of beta-lactam and macrolide antibiotics has probably caused a gradual increase in the S pneumoniae MIC. This relative increase in the MIC (ie, intermediate resistance or relative resistance) can be overcome by using full recommended doses of beta-lactams.
Most cases of penicillin-resistant S pneumoniae infection are still treated with penicillin. Most strains have increased MICs but are still susceptible and are not clinically resistant to penicillin.
Penicillin resistance is classified according to MICs. Breakpoints are as follows:
Sensitive - 0.6 µg/mL or less
Intermediate resistance - 0.1-1 µg/mL
Highly resistant - 2 µg/mL or more
Strains of pneumococci that are highly resistant to penicillin may be treated with levofloxacin, the only quinolone indicated for the treatment of highly penicillin-resistant S pneumoniae. Alternatively, vancomycin, clindamycin, or linezolid may be used.
The use of non-C cell-wall active agents against S pneumoniae, such as doxycycline or levofloxacin, does not increase penicillin resistance among pneumococci.
The widespread use of macrolides and trimethoprim-sulfamethoxazole (TMP-SMX) and tetracycline (excluding doxycycline) has been associated with penicillin-resistant S pneumoniae and multidrug-resistant S pneumoniae.
Most oral cephalosporins, except cefprozil, have been associated with increased S pneumoniae resistance. Use of intravenous-to-oral switch programs is as follows:
Most patients with CAP who are admitted to the hospital are treated with empiric intravenous antibiotic therapy. Unless these patients are acutely ill in the ICU or are unable to absorb medication from the gastrointestinal tract, they may be switched to equivalent oral therapy to complete a 2-week course of therapy after 48 hours.
Candidate agents for intravenous-to-oral switch programs have the same spectrum as intravenous agents, excellent bioavailability, few adverse effects, low resistance potential, and relatively low cost. Ideal agents for intravenous-to-oral switch programs include a respiratory quinolone or doxycycline.
Other agents that may be used if S pneumoniae is not the etiologic agent include azithromycin or clarithromycin.Empiric therapy in hospitalized patients with community-acquired pneumoniaSuboptimal regimens include the following:

Monotherapy
Ceftriaxone
Covers typical pathogens but not atypical pathogens
Adverse effects - Non– Clostridium difficile diarrhea, pseudobiliary lithiasis
1 g IV q24h
Azithromycin
Fails to cover approximately 25% of S pneumoniae strains
Should not be used alone
Covers atypical pathogens
Adverse effects - Nausea, vomiting, non– C difficile diarrhea
Very low serum levels - Slow onset/delayed therapeutic effect
Moderately expensive
Combination therapy
Ceftriaxone plus erythromycin
Covers typical and atypical organisms
Adverse effects - Nausea, vomiting, non– C difficile diarrhea, phlebitis, cardiac effects (QTc), pseudobiliary lithiasis
Most expensive combination

Intravenous-to-oral switch therapy - Disadvantage of double-drug therapy (relatively expensive/inconvenient)
Ceftriaxone plus azithromycin
Covers typical and atypical pathogens
Adverse effects - Nausea, vomiting, non– C difficile diarrhea, phlebitis, cardiac effects (QTc), pseudobiliary lithiasis
Intravenous-to-oral switch therapy - Disadvantage of double-drug therapy (relatively expensive/inconvenient)Optimal regimens include the following:
Monotherapy
Typical CAP pathogens
Respiratory quinolone
Ceftriaxone
Ertapenem
Typical CAP pathogens
Respiratory quinolone
Doxycycline

Empiric therapy for CAP in patients with HIV infection is as follows:
CAP in a patient with focal infiltrate on chest radiography and a CD4 count that exceeds 200 cells/µL
The most likely pathogens include S pneumoniae, H influenzae, M legionella, or C pneumoniae.
Optimal empiric therapy in the context of extrapulmonary findings (atypical pathogens) is with respiratory quinolone or doxycycline. In the absence of extrapulmonary findings (typical bacteria), ceftriaxone, doxycycline, respiratory quinolone, or ertapenem should be used. In patients with CAP who have features of both typical and atypical pathogens, respiratory quinolone or doxycycline should be used.
CAP in a patient with focal infiltrate on chest radiography and a very low CD4 count (<200 cells/µL)
The most likely pathogens include P jiroveci, M tuberculosis, Mycobacterium avium-intracellulare, and Histoplasma capsulatum.
Optimal empiric therapy for tuberculosis consists of isoniazid, ethambutol, rifampin, or pyrazinamide. M avium-intracellulare infections are treated with azithromycin plus ethambutol and/or rifampin, rifabutin, or azithromycin plus ethambutol plus respiratory quinolone. Histoplasmosis is treated with itraconazole or amphotericin B.

Consultations
Patients with severe CAP should have the benefit of an infectious disease specialist to assist in the underlying cause of severe CAP.
Diet
Diet in patients with CAP is as tolerated.
Activity
Patients with mild CAP may be treated in an ambulatory setting. Guide activity with common sense.
Medication
Before the role of atypical pathogens was appreciated, most patients with community-acquired pneumonia (CAP) were treated with a parenteral beta-lactam antibiotic. Approximately 15% of patients with possible atypical pneumonias were treated empirically with erythromycin or doxycycline.
Approximately 85% of CAP cases are caused by typical pathogens, such as S pneumoniae, H influenzae, or M catarrhalis, and approximately 15% are due to the nonzoonotic atypical pathogens, such as Legionella species, Mycoplasma species, or C pneumoniae. Atypical pathogens, such as Legionella species, were found to be important causes of CAP. Because clinicians could not clinically differentiate typical pneumonias from atypical pneumonias, combination therapy with a beta-lactam, such as ceftriaxone, in addition to erythromycin to cover both typical and atypical pathogens, became popular.
Although clinically differentiating the typical from the atypical pneumonias with a reasonable degree of certainty is possible, many clinicians empirically treat patients with CAP for both atypical and typical pathogens. Presently, a preferred therapeutic approach to CAP is monotherapy with a respiratory quinolone such as levofloxacin.
The severity of CAP determines the route of antibiotic administration (ie, oral for mild cases, intravenous for moderate-to-severe cases), predicts the necessity of admission to an ICU, predicts the duration of hospital stay, and contributes to the prognosis.
Because patients with CAP have the same pathogen distribution regardless of clinical severity, the empiric antibiotic treatment for CAP does not vary.
Because the severity of CAP is determined by cardiopulmonary or splenic function, using different antibiotics for severe or less severe cases of CAP or adding additional antibiotics because the patient has severe CAP is illogical. Antimicrobial therapy is directed against the microorganism and does not improve cardiopulmonary or splenic function, regardless of the degree of severity.

Blogger Comment:
Mild or walking pneumonia is commonly treated with levaquin 750 mg daily 7-10 days. Same as in severe sinusitis. Mild sinusitis, bacterial pharyngitis and acute bronchitis are commonly treated with zithromax or z-pack or biaxin.
Pneumonia requiring hospital admission is treated with levaquin IV 750 mg daily or alternatively IV rocephin 1 gram daily with zithromax 500 mg IV daily. Both regimens will cover most typical and atypical pneumonias. Levauin should not be combined with zithromax it add nothing to therapy and can cause prolonged QT interval. Combining Levaquin with reocephin is sometimes used in severe pneumonia. After 48 hours of good response to IV antibiotics patient can be discharged on oral antibiotics for 2 weeks. How the patient look clinically, vitals signs O2 saturation all determine when to switch to oral antibiotics and discharge. Blood culture and sputum culture are usually done in admission and direct treatment further legionela antigen in urine is usually ordered in patients with extrapulmonary findings like diarrhea, abdominal pain myalgias and hyponatermia. Cxr usually is not repeated unless patient do not respond or there are other concerns by radiologist of underlying malignancy. CXr improvement usually lags behind clinical improvement however by 2 weeks many patients show significant improvement.