Antibacterials for

Respiratory Tract Infections

Cecilia C. Maramba-Lazarte, MD, MScID
 Viral Respiratory Infections
• Many respiratory diseases may be viral in
origin and not require any antibiotic
• Rhinovirus
• Adenovirus
• Rubeolla
• Coronaviruses
• Parainfluenza viruses
Choice of Antibiotics for Bacterial Infections
• Efficacy –
Based on target pathogens-
local epidemiology
age
severity of illness/clinical presentation
co-morbidities
hospital acquired/community acquired
Based on prevailing resistance patterns in
the locality
• Safety
• Cost
 Bacterial Respiratory Infections
Common Diseases Common Etiologies
• Pharyngitis • Group A streptococcus
• Otitis Media • Strep pneumoniae
• H. influenzae
• Epiglotitis
• Staph aureus
• Bronchitis
• Pseudomonas
• Sinusitis aeruginosa, other gram
• Pneumonia negative org
• Lung Abscess • Anaerobes
•Atypical pathogens-
mycoplasma, chlamydia,
legionella
 Antimicrobial (%)Resistance by Disc Diffusion,
DOH Antimicrobial Resistance Surveillance
Jan-Dec 2008, Philippines
ARI Pathogens
Ampi Chloro Coamox Cotri Erythro Pen
iclav
Strep 4.8 21.7 0
pneumoniae
H. influenzae 17.4 20.9 38.5
M. 24.2 17.1 47.6 45.9
catarrhalis
 Antimicrobial (%)Resistance by Disc Diffusion,
DOH Antimicrobial Resistance Surveillance
Jan-Dec 2008, Philippines

Staphylococci

Ampi Pen Cipro Cotri Erythro Oxa Vanco

S. aureus 95.6 5.5 5.3 9.2 44.8 0

 Antimicrobial (%)Resistance by Disc Diffusion,
DOH Antimicrobial Resistance Surveillance
Jan-Dec 2008, Philippines

Pseudomonas aeruginosa

Ciprofloxacin
Ceftazidime

Tobramycin
Gentamicin

Piper-Tazo
Imipenem

Netilmicin
Cefepime
Amikacin

Pseudomonas 11.5 11.2 15.4 22.1 20.6 13.5 0 15.8 19.2

aeruginosa
 Recommended Antibiotics in Pediatric
CAP
Suspected Organisms Empiric Therapy Alternative
therapy
0-2 mos Gram (-) bacili Ampicillin + 3rd Gen Ceph +
Aminoglycoside Amino

3 mos-5 H. influenzae Mild Amoxycillin 2nd or 3rd Gen

yrs S.pneumoniae Ceph
Severe Penicillin G
S. aureus
Very Chloramphenicol 3rd Gen Ceph
severe
>5 yrs S. pneumoniae Pen G 2nd or 3rd Gen
Ceph

Hospital Gram (-) bacilli, S. Ceftazidime Piperacillin-

acquired aureus tazobactam
Algorithm for the risk stratification of CAP
among immunocompetent adults
Empiric Therapy for Adult CAP
Empiric Therapy for Adult CAP
Empiric Therapy of Adult CAP
Review of Antibiotics
Penicillin Route of Spectrum of Activity
Use
Natural Penicillins Active against most streptococci,
Penicillin G, K or Na IV, IM pneumococci, meningococci, oral
Benzathine Penicillin IM anaerobes, spirochetes, listeria,
Penicillin VK PO Corynebacterium spp. poor against
gram-negative rods; susceptible to
hydrolysis by β-lactamases
Antistaphylococcus penicillins Active against staphylococci (including
Oxacillin IM, IV β-lactamase producing strains) and
Cloxacillin PO streptococci and most gram positive
cocci; inactive against enterococci,
anaerobic bacteria and Gram negative
bacteria
Aminopenicillins Similar to Natural penicillins but has
Ampicillin IV, IM activity against some Gram negative
Amoxicillin PO bacteria (community acquired H.
influenzae, and E.coli)
Penicillin Route of Spectrum of Activity
Use
Extended spectrum penicillins Wider coverage for Gram
Carbenicillin negative bacteria including
Ticarcillin IV Pseudomonas aeruginosa,
Piperacillin IV active against enterococci,
Bacteroides spp.
Beta lactam-Beta lactamase Widens coverage of basic
inhibitor combination penicillin to include Staph
Amoxicillin-clavulanic PO aureus, increases gram
acid negative and anaerobic
Piperacillin- IV coverage
tazobactam
Ticarcillin- IV
clavulanic acid
 Pharmacokinetics of Penicillins

Antibiotic Oral Protein Metaboliz Urinary Aprox.

Bioavailabilit Binding ed (%) Recovery half-life in
y (%) (%) (%) adults
(hrs)
Pen G - 60 10-30 60-90 0.5-0.75
`Pen VK 60-73 80 10-30 20-40 0.5-1
Ampicillin 50 15-18 10 90 1-1.8
Amoxicillin 74-92 20 17-20 60-75 0.7-1.4
Clavulanate Well absorbed 25 ? 25-40 1

Oxacillin 30-35 90-94 45 55-60 0.4-0.7

Cloxacillin 50 95 20 30-60 0.5-1
Ticarcillin - 45-60 15 60-80 1.0-1.2
Piperacillin - 16 20-30 60-80 0.6-1.2
 Adverse effects of Penicillins
Adverse effects Frequenc Most
y% Frequent
GI disturbances (diarrhea, abdominal 2-5 Amp,
pain, vomiting) Amox clav
Hematologic toxicity (neutropenia, 1-4 Pen G, Oxa,
platelet dysfunction, hemolytic Pip
anemia)
Elevated liver function test 1-4 Oxa
Renal toxicity (interstitial nephritis, 1-2 Meth
hemorrhagic cystitis)
.2-0.05 Pen G
allergic reactions anaphylaxis, skin
rashes, fever, delayed type of serum
sickness
CNS toxicity (seizures, bizarre rare Pen G
sensations)
 Classification of Cephalosporins
Generation Prototype Drugs Useful Spectrum*
First Cefazolin (IV) Gram positive Streptococci, Staph
Cephalexin (PO) aureus; some gram negative
Second Cefuroxime (IV, PO) Community acquired E. coli, Klebsiella,
Cefaclor (PO) Proteus, H. influenzae, M. catarrhalis.
Cefoxitin (IV, IM) Less active against gram positive bacteria
Has added activity against Bacteroides
fragilis
Third Ceftriaxone (IV, IM) Enterobacteriaceae, Serratia, Neisseria
Cefotaxime (IV) gonorrhea; less active than 1st gen
Cefixime (PO) against Gram positive cocci
Ceftazidime (IV, IM) - also active against Pseudomonas
aeruginosa
Fourth Cefepime (IV, IM) Comparable to 3rd gen but more stable to
 lactamases of Gram negative bacteria
Fifth Ceftobiprole (IV, IM) Activity against MRSA, Gram negative
(not FDA approved) bacteria including Pseudomonas

*all cephalosporins have no activity against enterococci and listeria

 Pharmacokinetics of Selected Cephalosporins
Antibiotic Oral Protein Metabol Urinary Aprox. half-
Bioavailab Binding (%) ized (%) Recovery life in adults
ility* (%) (%/hr) (hrs)
1st Gen
Cephalexin 95 10-15 0 90/8 0.9-1.5
Cephradine 95 8-17 0 60-90/6 0.8-1.3
Cefazolin - 74-86 0 80-100/24 1.5-2.5
2nd Gen
Cefaclor 95 25 0 60-85/8 0.5-1.0
Cefuroxime axetil 37/52 33-50 0 50/12 1-2
Cefuroxime - 33-50 0 96/24 1.2-1.9
Cefoxitin - 65-79 <5 85/6 0.75-1
3rd Gen
Cefixime 40-50 65 0 16/24 3-4
Cefotaxime - 31-50 30-50* 15-25/6 1-1.5
Ceftriaxone - 85-95 ? 33-67/24 5-9
Ceftazidime - 17 0 80-90/24 1-2
4th Gen
Cefepime - 16-19 15 85 2
Adverse effects of Cephalosporins

Hypersensitivity reactions – 1-3%; may

cross react with penicillins in 5-20%
 Hematologic- 1-5%
diarrhea- 2-5%
abn liver function tests- 1-7%
biliary sludge (ceftriaxone)- 20%
interstitial nephritis- rare
 Spectrum of Activity of Macrolides
Drugs Gram (+) Gram (-) Others
Erythromycin S. pneumoniae, N. gonorrhea,
S. pyogenes, Bordatella Mycoplasma
Clostridium, S. aureus, pertussis pneumoniae
C. diphtheriae Campylobacter
L. monocytogenes jejuni Chlamydia
Treponema pallidum pneumoniae
Clarithromyci S. pneumoniae, H. influenzae
n S. pyogenes, N. gonorrhea Chlamydia
Clostridium, S. aureus, M. catarrhalis trachomatis
Bordatella
C. diphtheriae pertussis Legionella
L. monocytogenes pneumophilia
Azithromycin S. pneumoniae, H. influenzae
S. pyogenes, N. gonorrhea
Clostridium, S. aureus, M. catarrhalis
C. diphtheriae Bordatella
L. monocytogenes pertussis
 Pharmacokinetics of Macrolides
Antibiotic Oral Protein Elimination Route Aprox
Bioavaila Binding half-life
bility* (%) Biliary Renal (hrs)
(%) excretio excretion
n

Erythromycin 30-65 70-90 Majority 2-15% 1.4-2

Clarithromyci 55 65-75 Minimal 20-40 % 3-7

n
Azithromycin 37 7-50 >50% 4.5% 11-14
(48-96
after steady
state)
Adverse effects of Macrolides

1. epigastric distress
2. allergic reactions (fever and
rashes),
3. cholestatic jaundice
4. Cardiovascular adverse reactions
-ventricular arrhythmias, prolongation
of the QT interval, bradycardia, and
hypotension with IV administration
Drug Interactions with Macrolides
• Macrolides are CYP1A2 and CYP3A3/4
inhibitors
• increases the hepatic metabolism of
other drugs leading to increased effects
and toxicities (e.g., dicumarol,
carbamazepine, digoxin, theophylline,
ergot, cyclosporine, triazolam, etc.)
 Spectrum of activity of Quinolones
according to Generation
Generation Drugs Pathogens wherein Quinolone has
Good Activity
First Nalidixic acid Urinary pathogens, Shigella
Second Ciprofloxacin, Gram negative(Salmonella, Shigella,
Ofloxacin E. coli, other Enterobacteriacae,
Pseudomonas, H. influenzae), few
gram positive, Mycoplasma,
Chlamydia, Legionella, mycobacteria
Third Levofloxacin, H. influenzae, Salmonella, Shigella, E.
Gatifloxacin* coli, other Enterobacteriacae,
Moxifloxacin Mycoplasma, Chlamydia, Legionella
Strep pneumoniae, Methicillin
Sensitive S. aureus, mycobacteria
 Pharmacokinetics of Quinolones
Generation Drugs T1/2 Absorption Metabolism Excretion
(hrs) (%)
First Nalidixic acid 6-7 Partially Renal
hepatic
Second Ciprofloxacin 4 69 Hepatic Renal
Ofloxacin 8-9 85-95 (including Renal
CYP1A2)

Third Levofloxacin 6-8 99 Renal Renal

Moxifloxacin 12 86-92 Hepatic Hepatic
(glucoronide
and sulfate
conjugation)
 Adverse Effects of Quinolones
• nausea, vomiting, diarrhea; delirium, headache,
hallucinations, seizures; skin rashes, photosensitivity.
• Arthropathy has been documented in immature animals
thus damage may occur in growing cartilage in <18 yrs
• for the children -tx is limited to certain indications (Shigella
gastroenteritis, multi-drug resistant tuberculosis) or for
compassionate use only when other safer antibiotics are
inappropriate.
• Gatifloxacin, levofloxacin, and moxifloxacin should be
avoided in patients with known QTc interval prolongation or
uncorrected hypokalemia because QTc prolongation may
occur
• Gatifloxacin has been withdrawn in the US an&Philippines
because of with hyperglycemia in diabetic patients and with
hypoglycemia in patients also receiving oral hypoglycemic
agents.
 Drug Interactions with Quinolones
• Increased serum levels of quinolones may occur if it is given
concomitantly with probenecid.
• Quinolones enhances the anticoagulant effect of warfarin.
• Antacids (with aluminum and magnesium), iron, zinc and
sucralfate decreases absorption of quinolones.
• risk of tendon rupture is increased by corticosteroids.
• Increased risk of CNS adverse effects (e.g. seizures) occurs
with NSAIDS
• Most 3rd gen quinolones should be avoided when the patient
is given class IA (e.g., quinidine or procainamide) or class III
antiarrhythmic agents (sotalol, ibutilide, amiodarone); and in
patients receiving other agents known to increase the QTc
interval (e.g., erythromycin, tricyclic antidepressants).
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