Respiratory Infections
Upper respiratory infection
Most are viral: common cold, pharyngitis, rhinitis, sinusitis
etc.
Lower respiratory infection
Frequently viral
Bronchitis (or) asthma: cough, wheezing, dyspnea
Pneumonia: cough, fever, (chills), rapid respiration, dyspnea
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Marc Imhotep Cray, M.D.
Case 1
A 68-year-old man presents to the emergency department complaining of a
fever, dyspnea, and a cough productive of green sputum. Physical
examination reveals an ill-appearing man, breathing heavily.
On lung examination, you note bronchial breath sounds and dullness to
percussion over the right lower lung lobe. A chest x-ray demonstrates
circumscribed opacity over the region of his right lower lung lobe. You obtain
sputum and blood cultures and then admit this patient to the hospital for
antibiotic treatment.
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Marc Imhotep Cray, M.D.
Pneumonia: Overview
Pneumonia is a respiratory disease characterized by inflammation of lung
parenchyma (excluding bronchi) caused by viruses, bacteria, fungi, or
irritants
Treatment varies according to the situation
Le T and Bhushan V. First Aid for the USMLE Step 1 2015 (McGraw-Hill 2015)
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Marc Imhotep Cray, M.D.
Common causes of pneumonia
Neonates Children Adults Adults Elderly
(< 4 Wks.) (4 Wks.–18 Yrs.) (18–40 Yrs.) (40–65 Yrs.)
Group B Viruses (RSV) Mycoplasma S. pneumoniae S. pneumoniae
streptococci Mycoplasma C. pneumoniae H. influenzae Influenza virus
E. coli C. trachomatis S. pneumoniae Anaerobes Anaerobes
(infants–3 yr.) Viruses H. influenzae
C. pneumoniae Mycoplasma Gram-negative
(school-aged rods
children)
S. pneumoniae
Redrawn and modified from: Le T and Bhushan V. First Aid for the USMLE Step 1 2015
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Marc Imhotep Cray, M.D.
Lobar Pneumonia
S. pneumoniae most frequently, also Legionella, Klebsiella
Intra-alveolar exudate consolidation (A) may involve entire lobe (B) or lung
A B
Le T and Bhushan V. First Aid for the USMLE Step 1 2015 (McGraw-Hill 2015)
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Marc Imhotep Cray, M.D.
Bronchopneumonia
S. pneumoniae, S. aureus, H. influenzae, Klebsiella
Acute inflammatory infiltrates (C) from bronchioles into adjacent alveoli
patchy distribution involving ≥ 1 lobe (D)
C D
Le T and Bhushan V. First Aid for the USMLE Step 1 2015 (McGraw-Hill 2015)
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Marc Imhotep Cray, M.D.
Interstitial (atypical) pneumonia
Viruses (influenza, CMV, RSV, adenoviruses), Mycoplasma, Legionella,
Chlamydia
Diffuse patchy inflammation localized to interstitial areas at alveolar walls;
diffuse distribution involving ≥ 1 lobe (E)
Generally follows a more indolent course (“walking” pneumonia)
A B
Le T and Bhushan V. First Aid for the USMLE Step 1 2015 (McGraw-Hill 2015)
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Marc Imhotep Cray, M.D.
Companion Notes:
MedPharm Digital Guidebook 2015, UNIT 10 Drugs Used In Infectious Disease
eNotes Infectious Diseases Pharmacology
Rapid Review Antimicrobial Drugs and Vaccines
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Key Concepts
Antibiotics exploit differences between prokaryotic and
eukaryotic cells to promote specificity and limit toxicity
For example, bacterial enzymes involved in DNA replication
and RNA synthesis are different from those found in
eukaryotic cells
bacterial ribosome is also significantly different, allowing
selective targeting
Somers KD and Morse SA. Lange Flash Cards: Microbiology & Infectious Diseases. New York: McGraw-Hill, 2010
Marc Imhotep Cray, M.D.
1. Inhibition of cell wall synthesis
β-lactam antibiotics such as penicillin and cephalosporins
target peptidoglycan cross-linking by binding to and inhibiting
action of transpeptidase enzymes
Vancomycin inhibits cross-linking by binding terminal D-
alanine- D-alanine precursor and preventing transpeptidation
Cycloserine inhibits formation of D-alanine-D-alanine linkage
Bacitracin inhibits transport of new peptidoglycan precursors
through cell membrane
Isoniazid and ethionamide inhibit mycolic acid synthesis in
mycobacteria
5. Antimetabolites
Sulfonamides and trimethoprim inhibit folic acid metabolism
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Marc Imhotep Cray, M.D.
Antibacterials Summary Schematic
Marc Imhotep Cray, M.D. Johannsen EC. & Sabatine MS. PharmCards, 4th ed. Lippincott Williams & Wilkins, 2010 22
Antibiotic Resistance Mechanisms
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Antibiotic Resistance Mechanisms
Bacteria have evolved a number of mechanisms to protect themselves
from action of antibiotics Altered expression of proteins in drug-
resistant organisms
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“An Admonition” Mild, kind , yet earnest
reproof. Cautionary advice or warning.
“Learning the characteristics of antibiotics
simplifies learning infectious disease
pharmacotherapy. Students and clinicians who
attempt to learn the antibiotics of choice for
different types of infections before knowing the
characteristics of those drugs never truly
understand the context of what they are
attempting to learn. Once the characteristics
of the antibiotics are known, making a logical
choice to treat an infection is much easier.”
Gallagher JC, MacDougall C. Antibiotics simplified. 2nd Ed.
Jones & Bartlett Learning, 2012
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Pharmacology of Common Antibiotics
Used to Treat Bacterial Pneumonia
Penicillin
Azithromycin
Amoxicillin
Ciprofloxacin
Amoxicillin/clavulanate
Clarithromycin
Cefaclor
Erythromycin
Cefotaxime
Imipenem
Ceftazidime
Metronidazole
Ceftriaxone
Rifampin
Cefuroxime
Tetracycline
Cefuroxime axetil
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Marc Imhotep Cray, M.D.
Penicillins
EXAMPLES (in order of narrowest to broadest spectrum)
Natural penicillins – benzylpenicillin, phenoxymethylpenicillin
Antistaphylococcal penicillins – nafcillin, oxacillin
Aminopenicillins– ampicillin, amoxicillin
MECHANISM OF ACTION (MOA)
β lactam moiety binds to and inhibits transpeptidase required for
formation of peptidoglycan cross-links within bacterial cell wall results in
defective bacterial cell wall synthesis and subsequent cytolysis
Nafcillin & oxacillin are relatively resistant to staphylococcal β lactamases
Aminopenicillins have enhanced activity against aerobic Gram-negative
bacilli
Piperacillin when combined with tazobactam (a β-lactamase inhibitor) has
good activity against Pseudomonas spp.
Augmentin (or) Co-amoxiclav is a combination of amoxicillin and clavulanic
acid (a β lactamase inhibitor)
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Marc Imhotep Cray, M.D.
Penicillins cont. SIDE-EFFECTS
Urticarial rash
INDICATIONS Anaphylaxis
Pharyngitis/tonsillitis GI disturbance
Pneumonia Antibiotic-associated colitis
Otitis media Stevens–Johnson syndrome
Cellulitis Fever
Meningitis Joint pains
Endocarditis Rarely cholestatic jaundice w co-
Rheumatic fever amoxiclav
Osteomyelitis METABOLISM AND HALF-LIFE
UTI Elimination is via kidneys and biliary tract
CAUTIONS & CONTRA-INDICATIONS t½ for benzylpenicillin is ~30 min; t½ for
Hypersensitivity flucloxacillin is ~50 min; t½ for amoxicillin
(rashes, urticaria, angioedema, fever, is ~1h
arthralgia, acute interstitial nephritis (AIN) , MONITORING No specific drug
anaphylaxis) monitoring required 31
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Penicillins cont.
DRUG INTERACTIONS
Reduced efficacy of OCP when taking penicillins Women should be
warned of this and advised to use alternative contraceptive methods
IMPORTANT POINTS
Benzylpenicillin (penicillin G) must be administered parenterally because it
is inactivated by gastric acid secretions
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Penicillin Antibacterials Summary Table
MECHANISM OF ACTION:
MOA similar to penicillins except cephalosporins are relatively resistant to
staphylococcal β lactamases
o All beta-lactams share a MOA inhibition of transpeptidases (that is,
penicillin binding proteins) in the bacterial cell wall
Penetrate CSF poorly unless meningeal inflammation is present
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Cephalosporins and other β-lactams cont.
INDICATIONS SIDE-EFFECTS
Pneumonia Urticarial rash
Sepsis Anaphylaxis
Biliary tract infection GI disturbance
UTI Stevens–Johnson syndrome
Peritonitis Cholestatic jaundice (ceftriaxone)
Meningitis
DRUG INTERACTIONS
Reduced efficacy of OCP when taking cephalosporins women should be
warned and advised to use alternative contraceptive methods
IMPORTANT POINT
10% of patients who are hypersensitive to penicillins may have a similar
reaction to cephalosporins and other β lactams 37
Marc Imhotep Cray, M.D.
Beta-lactam Antibacterials (Other than PCN)
AP, anti-pseudomonal Johannsen EC. & Sabatine MS. PharmCards, 4th ed. Lippincott Williams & Wilkins, 2010
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Macrolides
EXAMPLES erythromycin, azithromycin, clarithromycin
MECHANISM OF ACTION
Inhibition of bacterial RNA-dependent protein synthesis by reversibly binding
to 50S subunit of ribosomes within organism This affects bacterial growth
and may be either bacteriostatic or bacteriocidal
INDICATIONS
Respiratory tract infections
Campylobacter enteritis
Urethritis (non-gonococcal)
Pertussis infection
Skin and soft tissue infections
Otitis media
Helicobacter pylori eradication
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Macrolides cont.
CAUTIONS & CONTRA-INDICATIONS METABOLISM & HALF-LIFE
Liver disease Metabolized in liver and excreted via
Hypersensitivity biliary route
t½ is variable – t½ for erythromycin is
SIDE-EFFECTS 1–1.5 h; t½ for azithromycin is 2–4
Nausea and vomiting days; t½ for clarithromycin is 3–7 h
Diarrhea
Hepatitis MONITORING No specific drug
Anorexia monitoring required
Pancreatitis
Headaches
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Macrolides cont.
DRUG INTERACTIONS
Enhanced anticoagulant effect of warfarin
Macrolides inhibit metabolism of theophylline thereby increasing plasma
levels
Increased plasma levels of carbamazepine with concomitant use of
macrolides
Increased risk of cardiac arrhythmias with amiodarone due to QT
prolongation
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Marc Imhotep Cray, M.D.
Macrolides cont.
IMPORTANT POINTS
Erythromycin has similar bacterial sensitivity to penicillins and therefore
can be used as an alternative in penicillin allergic patients
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Macrolides cont. Erythromycin
Inhibition of liver cytochrome P450 by erythromycin has led to serious
drug interactions
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Marc Imhotep Cray, M.D.
Macrolides cont. Azithromycin
Azithromycin has a half-life of more than 70 h, which allows for once-
daily dosing and a 5-d course of treatment for community-acquired
pneumonia
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Marc Imhotep Cray, M.D.
Metronidazole
MECHANISM OF ACTION
Metronidazole possesses a nitro-group that becomes charged and trapped
within intracellular compartment of anaerobes leads to bacterial DNA
damage and ultimately strand breakage cell death
INDICATIONS
Surgical prophylaxis
Anaerobic infections (including dental and abdominal sepsis)
Aspiration pneumonia
Protozoal infections
Pelvic inflammatory disease
IMPORTANT POINTS
Metronidazole is a potent inhibitor of obligate anaerobes and protozoa such
as Trichomonas spp. and Entamoeba spp.
Patients should be advised to completely avoid alcohol during and for 48 h
after a course of metronidazole due to the risk of a severe disulfiram-like
reaction (flushing and hypotension)
Metronidazole can be used in chronic renal failure however, it is rapidly
removed from plasma by dialysis
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Marc Imhotep Cray, M.D.
Quinolones
EXAMPLES Ciprofloxacin, levofloxacin, ofloxacin
MECHANISM OF ACTION
Bactericidal action of ciprofloxacin results from inhibition of both type II
(DNA gyrase) and type IV topoisomerases, required for bacterial DNA
replication, transcription, repair and recombination
INDICATIONS
UTI
Infections of the GI system
Bronchopulmonary infections
Typhoid fever
Gonorrhea and non-gonococcal urethritis and cervicitis
Anthrax
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Quinolones cont.
CAUTIONS AND CONTRA-INDICATIONS SIDE-EFFECTS
Patients with a history of tendon disorders GI disturbance
related to quinolones Headaches
Pregnancy, children and growing Dizziness
adolescents (due to risk of joint arthropathy) Rashes
Avoid in patients with CNS disorders (including Stevens–Johnson syndrome)
(e.g. epilepsy -can reduce seizure threshold) Tendon inflammation and
METABOLISM AND HALF-LIFE damage
t½ for ciprofloxacin is 3-6 h Confusion, anxiety and
Ciprofloxacin is excreted predominately depression
unchanged in urine Phototoxicity with excessive
sunlight
MONITORING No specific drug monitoring Seizures
required
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Marc Imhotep Cray, M.D.
Quinolones cont.
DRUG INTERACTIONS
Increased risk of nephrotoxicity when quinolones given with cyclosporin
Increased risk of torsades de pointes with other drugs that also prolong the
QT interval
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Tetracyclines
EXAMPLES Doxycycline, tetracycline, oxytetracycline
MECHANISM OF ACTION
Active uptake into a susceptible organism results in inhibition of
protein synthesis
Their bacteriostatic effect is achieved by binding to prokaryotic 30S
ribosomal subunit and inhibiting aminoacyl tRNA and mRNA
ribosomal complex formation
DRUG INTERACTIONS
Tetracyclines can enhance effects of warfarin (due to enzymatic inhibition)
Risk of idiopathic intracranial hypertension when tetracyclines used with retinoids
Doxycycline can increase plasma concentrations of cyclosporine
IMPORTANT POINTS
Patients are advised to use high-factor sun protection and avoid direct sun exposure when
on doxycycline (due to photosensitivity)
Tetracyclines should be avoided in anyone taking potentially hepatotoxic drugs
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Marc Imhotep Cray, M.D.
Trimethoprim
MECHANISM OF ACTION METABOLISM AND HALF-LIFE
Binds to bacterial dihydrofolate reductase and Approximately 50% is bound to plasma
irreversibly inhibits production of protein
tetrahydrofolate a precursor for synthesis of t½ ranges from 8.6–17 h.
thymidine results in inhibition of bacterial Elimination is via kidneys
DNA synthesis
MONITORING No specific drug monitoring
INDICATIONS required
UTI
CAUTIONS AND CONTRA-INDICATIONS
. Blood dyscrasias
. Caution in patients with renal impairment
SIDE-EFFECTS
. GI disturbance
. Pruritis
. Rashes
. Hyperkaliemia
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Trimethoprim cont.
DRUG INTERACTIONS
Increased risk of ventricular arrhythmias with amiodarone
Increased risk of nephrotoxicity when given with cyclosporine
Increased risk of hematological toxicity when given with azathioprine and
methotrexate
IMPORTANT POINTS
Commonly sensitive organisms include Gram-positive aerobes
(Staphylococcus spp.) and Gram-negative aerobes (Enterobacter spp.,
Haemophilus spp., Klebsiella spp.)
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Co-trimoxazole
A combination of trimethoprim
and sulfamethoxazole which
inhibits an earlier stage of
tetrahydrofolate synthesis
o Drug of choice in the treatment
of Pneumocystis jiroveci
pneumonia
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In Re of community acquired pneumonia (CAP)
It is often difficult to establish a definite cause of community acquired
pneumonia (CAP)
More than 80% of cases are caused by typical pathogens such as S
pneumoniae, H influenzae, or M catarrhalis, and 15% are due to
nonzoonotic atypical pathogens such as Legionella species,
Mycoplasma species, or C pneumoniae
Currently, monotherapy coverage of both typical and atypical pathogens in
CAP is preferred to double-drug therapy
Preferred initial therapy includes a macrolide, doxycycline, or a
quinolone active against respiratory pathogens
Second-line antibiotics
Doxycycline, clarithromycin
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Treatment of bacterial pneumonia cont.
Type of infection
With comorbidity
Mixed infections with S. pneumoniae, H. influenzae, oral
anaerobes, Gram negative bacilli, S. aureus, Legionella sp.
First-line antibiotics
Cefaclor, cefuroxime axetil, amoxicillin/clavulanate or any
of these plus erythromycin or clarithromycin
Second-line antibiotics
Trimethoprim/sulfamethoxazole plus erythromycin
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Treatment of bacterial pneumonia cont.
Type of infection
When community acquired severe disease in hospital, with
or without comorbidity S. pneumoniae, H. influenzae,
Legionella sp., M. pneumoniae, S. aureus, C. pneumoniae
Comorbidity pathogens: anaerobes, Gram negative bacilli
First-line antibiotics
Cefuroxime axetil, cefuroxime, cefotaxime, ceftriaxone, or
any of these plus erythromycin or clarithromycin ± rifampin
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Marc Imhotep Cray, M.D.
Treatment of bacterial pneumonia cont.
Type of infection
With severe disease in ICU environment S. pneumoniae,
H. influenzae, Legionella sp., Gram-negative bacilli, P.
aeruginosa, S. aureus, M. pneumoniae, C. pneumoniae
First-line antibiotics
Erythromycin ± rifampin plus either ciprofloxacin,
imipenem, or ceftazidime
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Treatment of bacterial pneumonia cont.
Type of infection
In institutionalized elderly patients with mild to moderate
disease S. pneumoniae, H. influenzae, oral anaerobes,
Gram negative bacilli, S. aureus, Legionella sp.
First-line antibiotics
Trimethoprim/sulfamethoxazole, cefaclor, cefuroxime
axetil, amoxicillin/clavulanate, or any one of the above ±
erythromycin or clarithromycin
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Marc Imhotep Cray, M.D.
Treatment of bacterial pneumonia cont.
Type of infection
With severe disease S. pneumoniae, H. influenzae, oral
anaerobes, Gram negative bacilli, S. aureus, Legionella sp.
First-line antibiotics
Cefaclor or cefuroxime axetil or amoxicillin/clavulanate or
ceftriaxone or combinations, penicillin or amoxicillin plus
ciprofloxacin
Second-line antibiotics
Ciprofloxacin plus clindamycin
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Marc Imhotep Cray, M.D.
Treatment of bacterial pneumonia cont.
Children
Type of infection
With mild disease S. pneumoniae, S. aureus, streptococci
Group A, M. pneumoniae, H. influenzae
First-line antibiotics
Amoxicillin, erythromycin estolate
Second-line antibiotics
Trimethoprim/sulfamethoxazole, clarithromycin,
erythromycin/sulfisoxazole, amoxicillin/clavulanate, cefixime,
cefaclor, cefuroxime axetil chloramphenicol ± erythromycin or
clarithromycin
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Marc Imhotep Cray, M.D.
Treatment of bacterial pneumonia cont.
Children
Type of infection
With severe disease S. pneumoniae, S. aureus,
streptococci Group A, M. pneumoniae, H. influenzae
First-line antibiotics
Cefuroxime ± erythromycin estolate or clarithromycin
Second-line antibiotics
Trimethoprim/sulfamethoxazole, clarithromycin,
erythromycin/sulfisoxazole, amoxicillin/clavulanate, cefixime,
cefaclor, cefuroxime axetil, chloramphenicol ± erythromycin or
Marc Imhotep Cray, M.D.
clarithromycin 68
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Marc Imhotep Cray, M.D.
Further study:
eLearning (IVMS Cloud Folders)
Pharmacology
Infectious Disease
Microbial biology & Immune System
Textbooks:
Batchelder A. et al. Rapid Clinical Pharmacology- A Student Formulary. 1st
ed. John Wiley & Sons, 2011
Carroll KC etal. Jawetz, Melnick, & Adelberg’s Medical Microbiology 27th
Ed. New York: McGraw-Hill, 2016
Gallagher JC, MacDougall C. Antibiotics simplified. 2nd Ed. Jones & Bartlett
Learning, 2012
Ryan KJ and Ray CG Eds. Sherris Medical Microbiology, 5th Ed. New York:
McGraw-Hill, 2010
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