Pneumonia

Dr. Layla Borham

Objectives

By the end of the lecture you are able to:

• Define pneumonia.

• Know classification of pneumonia.

• Describe the different antimicrobial regimens

used for treatment of pneumonia.

Dr. Layla Borham

Clinical Case • A 15 year old female with a history of hay fever develops fever,

headache and malaise for 4 days followed by a nonproductive cough

and scratchy throat.

• On examination, her temperature is 28.5°C, pulse 90 beats/min, BP

110/70, respiratory rate 20 beats/min.

• Physical examination is unremarkable except for scattered rales over

the left lower lung. Chest X ray reveals a patchy left lower lobe

infiltrate. Diagnosis was pneumonia. Erythromycin was prescribed.

• What is erythromycin? what other antimicrobials used in pneumonia?

• If she is taking antihistamines, what drug interaction might occur?

Dr. Layla Borham

4 Dr. Layla Borham

• Infection of the alveoli, distal airways, and

interstitium.

Classification

• Community-acquired pneumonia (CAP)

• Healthcare-acquired pneumonia (HCAP)

1. Hospital-acquired pneumonia (HAP)

2. Ventilator-associated pneumonia (VAP)

Pneumonia • Treatment of pneumonia depends largely on the empiric use of

antibiotic regimens directed against potential pathogens.

• Direct the use of antibiotic agents in bacterial pneumonia based on

laboratory data as well as clinical response.

• The possibility of Legionella infection should always be considered

when evaluating CAP, because delayed treatment significantly

increases mortality.

• The most prevalent causative organism is Streptococcus

pneumoniae, regardless of the host or the setting; empiric therapy

must be selected with this consideration in mind. Dr. Layla Borham

Drugs used in the treatment of Pneumonia

Dr. Layla Borham

Pneumonia

• A prudent course of action for empiric outpatient

therapy is to include:

(1) One of the macrolide agents plus a second- or third-

generation cephalosporin or amoxicillin and

clavulanate or

(2) Trimethoprim and sulfamethoxazole (TMP-SMZ) as a

single agent.

Dr. Layla Borham

Pneumonia

• Patients who have moderate clinical impairment or co-

morbidity are best treated with parenteral agents:

(1) Macrolide plus a second-generation or third-

generation cephalosporin, (as single agents) or

(2) Ampicillin and sulbactam (Unasyn), or

(3) Piperacillin and tazobactam (Zosyn), or

(4) Ticarcillin and clavulanate (Timentin).

Dr. Layla Borham

I. Macrolides

Azithromycin, Clarithromycin, Erythromycin

• Macrolide acts by inhibition of protein synthesis to arrest

bacterial growth.

• Macrolides provide the best coverage for the most likely

organisms in community-acquired bacterial pneumonia (CAP).

• It is the initial drug of choice, as they have effective coverage

for gram-positive, Legionella, and Mycoplasma organisms.

• Newer macrolides Azithromycin has better action against H

influenzae compared with erythromycin, and offers improved

compliance because of reduced dosing frequency and less GIT

adverse effects. Dr. Layla Borham

II. Cephalosporins • Second-generation cephalosporins (Cefprozil, Cefaclor, and

Cefuroxime) provide adequate activity against Gm +ve organisms.

• Third-generation cephalosporins (Cefotaxime, Ceftazidime,

Ceftriaxone) have wider activity against most gram-negative

bacteria, including beta-lactamase–producing strains and may be

effective against ampicillin-resistant S pneumoniae.

• IV cephalosporins may be combined with a macrolides. They

broaden the gram-negative coverage, and in the case of third-

generation agents, they may be effective against resistant S

pneumoniae. Dr. Layla Borham

• Cefepime is the best beta-lactam for IM administration.

This agent is a fourth-generation cephalosporin that has

gram-negative coverage comparable to ceftazidime but

with better gram-positive coverage (comparable to

ceftriaxone).

• Ceftaroline fifth-generation cephalosporins indicated

for community-acquired bacterial pneumonia.

• Activity against aerobic and anaerobic gram-positive

and aerobic gram-negative bacteria.

Dr. Layla Borham

III. Aztreonam (Azactam) • It is a monobactam, not a beta-lactam, antibiotic that

inhibits cell wall synthesis during bacterial growth.

• This agent has activity against gram-negative bacilli

but very limited gram-positive activity, and it is not

useful for anaerobes.

• It may be used in patients allergic to penicillins or

cephalosporins.

• As with all antibiotics eliminated by the kidneys, obtain

estimates of the CrCl, and make appropriate dosage

modifications. Dr. Layla Borham

IV. Fluoroquinolone: Ciprofloxacin • Fluoroquinolone that inhibits bacterial DNA synthesis

and, consequently, growth, by inhibiting DNA gyrase

and topoisomerases.

• Quinolones have broad activity against gram-positive

and gram-negative aerobic organisms but no activity

against anaerobes.

• Continue ciprofloxacin treatment for at least 2 days (7-

14 d typical) after the patient's signs and symptoms have

disappeared.

Dr. Layla Borham

V. Clindamycin

• Lincosamide semisynthetic antibiotic inhibits bacterial

growth, possibly by blocking protein synthesis.

• Clindamycin is also effective against aerobic and

anaerobic streptococci (except enterococci).

• Clindamycin is available in parenteral and oral form.

Dr. Layla Borham

VI. Carbapenem Ertapenem, Imipenem and cilastatin

• Carbapenem antibiotics that has bactericidal activity

resulting from inhibition of cell wall.

• Ertapenem is indicated for community-acquired

pneumonia due to S pneumoniae (penicillin-susceptible

isolates only).

• Imipenem and cilastatin used for treatment of multiple

organism infections. Use this agent with caution in the

presence of renal insufficiency. Dr. Layla Borham

Meropenem • It is indicated for community-acquired pneumonia,

including multi–drug-resistant S pneumoniae.

• A bactericidal broad-spectrum carbapenem antibiotic

that inhibits cell wall synthesis.

• It is effective against most gram-positive and gram-

negative bacteria and has slightly increased activity

against gram-negatives and slightly decreased activity

against staphylococci and streptococci compared with

imipenem. Dr. Layla Borham

VII. Sulfamethoxazole and trimethoprim

• This agent inhibits bacterial synthesis of dihydrofolic acid by

competing with paraaminobenzoic acid, thereby inhibiting

folic acid synthesis and resulting in inhibition of bacterial

growth.

VIII. Amoxicillin and clavulanate

• Alternative agent for patients who are allergic or intolerant

to macrolides.

• Amoxicillin inhibits bacterial cell wall synthesis. The

addition of clavulanate inhibits beta-lactamase producing

bacteria. Dr. Layla Borham

Ampicillin and sulbactam

• It is a combination of beta-lactamase inhibitor with

ampicillin that is used as an alternative to amoxicillin.

Piperacillin and tazobactam

Ticracillin and clavulanate

• Antipseudomonal penicillin plus beta-lactamase

inhibitor. Good coverage against most gram-positive,

most gram-negative, and most anaerobic bacteria

• Monitor liver and kidney functions and do CBC.

Dr. Layla Borham

IX. Linezolid • Oxazolidinone antibiotic that prevents protein synthesis.

• It is used as an alternative drug in patients allergic to vancomycin

and for treatment of vancomycin-resistant enterococci. It is also

effective against MRSA and penicillin-susceptible S pneumoniae

infections.

• Linezolid is bacteriostatic against enterococci and staphylococci

and bactericidal against most strains of streptococci.

• Linezolid may increase serotonin CNS levels as a result of MAO-

A inhibition, increasing the risk of serotonin syndrome.

Dr. Layla Borham

X. Vancomycin

• It inhibits cell wall synthesis

• It has excellent gram-positive coverage, including

methicillin-resistant S aureus (MRSA).

• Use CrCl to adjust the dose in patients diagnosed with

renal impairment.

Dr. Layla Borham

XI. Doxycycline

• It inhibits protein synthesis and, thus, bacterial growth.

• A broad-spectrum, synthetically derived bacteriostatic

antibiotic in the tetracycline class.

• Doxycycline is an alternative agent for patients who

cannot tolerate macrolides or penicillins.

Dr. Layla Borham

Combination drugs • The combination of trimethoprim and sulfamethoxazole (TMP-

SMZ) may be used in the patient with pneumonia and a history of

chronic obstructive pulmonary disease (COPD) or smoking.

• Severely ill patient with features of sepsis and/or respiratory

failure, and/or when neutropenia is known or suspected, treatment

with an IV macrolide is combined with an IV third-generation

cephalosporin and vancomycin.

• An alternative regimen may include imipenem, meropenem, OR

piperacillin and tazobactam plus a macrolide and vancomycin.

• Fluoroquinolones, including levofloxacin, moxifloxacin, and

gatifloxacin, may also be used. Dr. Layla Borham

Community

acquired.

(outpatient

therapy) Adult

patient

XR = Extended

Release

Outpatient

No co-morbidities:

Azithromycin 500 mg x1, then 250 mg once daily OR

azithromycin 2 gm (XR) x 1 dose (OR)

Clarithromycin 500mg orally twice daily or 1gram (XR) orally

once daily x 7 days (OR)

Doxycycline100mg orally twice daily

Co-morbidities present:

Levofloxacin750 mg once daily x 5 days (OR)

mofloxacin 400mg po qd x 7-10days (OR)

Azithromycin500 mg x1, then 250 mg once daily PLUS

[Augmentin XR* 1000/62.5 mg 2 tablets orally twice daily OR

Cefdinir 300 mg orally twice daily OR Cefpodoxime 200 mg

orally twice daily OR Cefprozil 500 mg orally twice daily] x 7

days

*AUGMENTIN XR is contraindicated in patients with a

creatinine clearance of < 30 mL/min. and in hemodialysis patients Dr. Layla Borham

Pneumonia

Community

acquired

Pneumonia

- Adult (any

age)

Hospitalized patient:

Azithromycin 500mg IV once daily PLUS Ceftriaxone1 gram q24h

(OR)

Azithromycin500mg IV once daily PLUS Ertapenem 1 gram q24h

(OR)

Monotherapy:

Levofloxacin750 mg IV/PO once daily (OR)

Moxifloxacin 400mg IV qd.

ICU patient (CAP):

Ceftriaxone1-2 grams IV q24h OR

Ampicillin-sulbactam(Unasyn) 1.5-3.0 grams ivpb q6h] PLUS

[Azithromycin500mg IV once daily OR Levofloxacin750 mg IV/PO

once daily

(OR)

Moxifloxacin 400mg IV qd.] PLUS Vancomycin - (patient-specific

regimen - trough goal 15-20 mcg/ml) Dr. Layla Borham

Hospital-

acquired

Pneumonia

(HAP)

(nosocomial)

Multi-drug resistance unlikely

Ceftriaxone1-2 grams IV q24h OR

Ampicillin-sulbactam(Unasyn) 3.0 grams ivpb q6h OR

Levofloxacin750 mg IV/PO once daily

Multi-drug resistance LIKELY

Piperacillin-tazobactam3.375g ivpb q6h OR

Cefepime2 grams IV every 12 hours OR

Meropenem 1 gm IV q8h OR

Doripenem 500 mg IV q8h

PLUS (If MRSA suspected)

Vancomycin - (patient-specific regimen - trough goal 15-20

mcg/ml)

Dr. Layla Borham

Aspiration

pneumonia

Community acquired:

Clindamycin 600mg ivpb every 6 to 8 hours OR

Augmentin 875mg PO bid or 500mg tid x 10 days

Hospital acquired:

Piperacillin-tazobactam3.375g ivpb q6h OR

Ampicillin-sulbactam (Unasyn) 1.5-3.0 grams ivpb q6h. OR

Cefoxitin2 grams ivpb q6-8h or Cefotetan1-2 grams IV q12h.

OR

[Cefotaxime2g ivpb q8h or Ceftriaxone2 grams ivpb q24h]

PLUS Clindamycin600mg IV q6-8h. OR

Clindamycin600mg IV q6-8h PLUS [Ciprofloxacin400mg IV

q12h or Levofloxacin500 - 750mg IV qd. ]

Hospital acquired:

(Cover most

common pathogens

+ possibility of

aspiration)

Piperacillin-tazobactam 3.375 grams IV every 6 hours PLUS

Ciprofloxacin 400mg IV q12h OR

Cefepime2 grams IV every 12 hours PLUS

Clindamycin600mg IV every 6 hours. Dr. Layla Borham

Ventilator-associated pneumonia (VAP)

Mild to

moderate

infection AND

multi-drug

resistance

unlikely):

Ceftriaxone1-2 grams IV q24h OR

Ampicillin-sulbactam(Unasyn) 3.0 grams ivpb q6h OR

Levofloxacin750 mg IV/PO once daily OR

Ertapenem 1 gm IV q24h

PLUS (If MRSA suspected)

Vancomycin - (patient-specific regimen - trough goal 15-20

mcg/ml)

(Severe infection

OR multi-drug

resistance

LIKELY):

Cefepime2 grams IVevery 12 hours OR

Piperacillin-tazobactam4.5 grams IV Q6H OR

Meropenem 1 gm IV q8h

PLUS

Vancomycin - (patient-specific regimen - trough goal 15-20

mcg/ml)

PLUS

Ciprofloxacin400mg IV q8h OR

Levofloxacin750 mg IV/PO once daily OR

Aminoglycoside (Tobra) - patient-specific regimen. Dr. Layla Borham

Pneumonia

• Duration of treatment:

1. Community acquired-mild: 7-10days.

2. Gram negative (usually nosocomial): 3 to 6

weeks.

3. Staphylococcal: 3 to 4 weeks

4. Legionella, mycoplasma, chlamydia: 14 to 21

days.

5. Lung abscess: 4 to 6 weeks.

Basic Pharmacodynamics of Antimicrobial Drugs

Mechanism of

Action Toxicity

Aminoglycosides

Protein

synthesis, Cell

membrane leak

Nephrotoxic, NMJ block,

Ototoxic, Vestibular

Cephalosporins Cell Wall

Synthesis

Hypersensitivity, Immune

reactions, Drug Fevers

Fluoroquinolones DNA Gyrase

Cartilage damage (juveniles),

Skin rash, Stevens-Johnson

syndrome

Macrolides Protein

synthesis

GI intolerance, NMJ block,

Myocardial depression,

thrombophlebitis and

cholestatic hepatitis Dr. Layla Borham

Basic Pharmacodynamics of Antimicrobial Drugs

Mechanism of

Action Toxicity

Carbapemems Cell Wall

Synthesis

GIT, thrombophlebitis, allergy,

and impaired renal functions

Monobactams Cell Wall

Synthesis

Hypersensitivity, immune

reactions, drug fevers

Vancomycin Cell Wall

Synthesis

Nephrotoxicity, ototoxicity,

allergy and cytopenias, red

man syndrome

Clindamycin Protein synthesis

GI intolerance, NMJ block,

myocardial depression,

pseudomembranous colitis and

cutaneous hypersensitivity Dr. Layla Borham

Basic Pharmacodynamics of Antimicrobial Drugs

Mechanism of

Action Toxicity

Penicillins Cell Wall Synthesis Hypersensitivity

Sulfonamides Folic Acid Synthesis

Immune, Nephrotoxic,

Hemolytic anemia,

depression anemia

Tetracyclines Protein synthesis

Nephrotoxic, GI

irritation, Hepatotoxic,

Phototoxic, Dental/Bone

(juveniles)

Infectious

Diseases Society

of America

(IDSA)

guidelines for

treatment of

patients with

community-

acquired

pneumonia.