ANTIBIOTIK

Hal yg mendasari penggunaan

antimikroba

• Empiric therapy
 Awal pengobatan/pengalaman empiris/
butuh penanganan segera
• Definitive therapy
 Organisme penyebab infeksi telah diketahui
• Prophylaxis
 Mencegah timbulnya infeksi bakteri
 Dasar Pemilihan Antibiotik

• Konfirmasi keberadaan infeksi

• Identifikasi patogen
• Terapi empiris yg selektif dgn
pertimbangan faktor host dan obat
Konfirmasi keberadaan infeksi

• Gejala systemik
 Demam
 Peningkatan leukosit darah (WBC)
• Gejala lokal
 Erythema
 Purulent drainage
• Gejala pada organ spesifik
 Flank pain
 Stiff neck with severe headache
 Dasar Pemilihan Antibiotik

• Konfirmasi keberadaan infeksi

• Identifikasi patogen
• Terapi empiris yg selektif dgn
pertimbangan faktor host dan obat
 Identifikasi patogen

• Kultur kuman sebelum menggunakan

antibiotik
• Gram Stain: Pedoman terapi empiris
• Secara mikrobiologis utk identifikasi
mikroorganisme
• Tes sensitivitas antibiotik
 Bacteria by Site of Infection
Mouth Skin/Soft Tissue Bone and Joint
Peptococcus S. aureus S. aureus
Peptostreptococcus S. pyogenes S. epidermidis
Actinomyces S. epidermidis Streptococci
Pasteurella N. gonorrhoeae
Gram-negative rods

Abdomen Urinary Tract Upper Respiratory

E. coli, Proteus E. coli, Proteus S. pneumoniae
Klebsiella Klebsiella H. influenzae
Enterococcus Enterococcus M. catarrhalis
Bacteroides sp. Staph saprophyticus S. pyogenes

Lower Respiratory Lower Respiratory Meningitis

Community Hospital S. pneumoniae
S. pneumoniae K. pneumoniae N. meningitidis
H. influenzae P. aeruginosa H. influenza
K. pneumoniae Enterobacter sp. Group B Strep
Legionella pneumophila Serratia sp. E. coli
Mycoplasma, Chlamydia S. aureus Listeria
 Identifikasi patogen

• Kultur kuman sebelum menggunakan

antibiotik
• Gram Stain: Pedoman terapi empiris
• Secara mikrobiologis utk identifikasi
mikroorganisme
• Tes sensitivitas antibiotik
 Anaerobes

Above Diaphragm Below Diaphragm

Peptococcus spp. Clostridium difficile,

Peptostreptococcus perfringens, tetani
spp. Bacteroides fragilis,
Prevotella disastonis, ovatus,
Veillonella thetaiotamicron
Actinomyces Fusobacterium
 Other Bacteria

Atypical Bacteria Spirochetes

Legionella pneumophila Treponema pallidum
Mycoplasma (syphilis)
pneumoniae, hominis Borrelia burgdorferi
Chlamydia pneumoniae, (Lyme)
trachomatis
 Identifikasi patogen

• Kultur kuman sebelum menggunakan

antibiotik
• Gram Stain: Pedoman terapi empiris
• Secara mikrobiologis utk identifikasi
mikroorganisme
• Tes sensitivitas antibiotik
 Test sensitivitas antibiotik

• Minimum Inhibitory Concentration (MIC) –

Konsentrasi terendah obat yg mencegah
pertumbuhan bakteri
 Susceptible: dosis antibiotik, akan mencapai
konsentrasi yg menghambat pertumbuhan
mikroorganisme.
 Intermediate: Dosis maksimal yg mencapai kadar
dlm serum dan jaringan yg mana kecepatan respon
mungkin lebih rendah daripada utk isolate yg sesuai.
 Resistant: Tdk akan mencapai kadar yg cukup untuk
menghambat infeksi
 Pertimbangan farmakodinamik
yg diperlukan ketika
meresepkan antimikroba

• Bacteriostatic: Menghambat
pertumbuhan kuman
• Bactericidal: Membunuh kuman

• Concentration-dependent killing
• Time-dependent killing
-Lactams
 -Lactam Characteristics
• MOA: menghambat sintesa dinding sel
• Bactericidal (exception: Enterococcus)
• Time-dependent killers
• Short t1/2
• Eliminasi melalui ginjal (exceptions:
nafcillin, oxacillin, ceftriaxone)
• Resistance: β-lactamase degradation
Decreased penetration
Chemical Structure: Allergenicity
 Natural Penicillins
(Penicillin G, Penicillin VK)

Gram-positive Gram-negative
Penicillin-susc S. aureus Neisseria spp.
Penicillin-susc S. pneumoniae
Group streptococci Anaerobes
Viridans streptococci Above the diaphragm
Enterococcus Clostridium spp.
(not difficile)

Other
Treponema pallidum (syphilis)
Penicillinase-Resistant Penicillins
(Nafcillin, Oxacillin, Dicloxacillin)

Dikembangkan utk mengatasi inaktivasi oleh

enzim penicillinase terhadap S. aureus

Gram-positive
Methicillin Susceptible S. aureus (MSSA)
Group streptococci
Viridans streptococci
 Aminopenicillins
(Ampicillin, Amoxicillin)
Dikembangkan utk meningkatkan aktifitas melawan
Gram-Negative aerobes
Gram-positive Gram-negative
PCN-Susp S. aureus Proteus mirabilis
PCN-Susp S. pneumoniae Listeria monocytogenes
Group streptococci Salmonella
Viridans streptococci Shigella
Enterococcus H. influenzae
S. pyogenes E. coli
 Antipsuedomonal Penicillins:
Carboxypenicillin
(Ticarcillin)
Dikembangkan utk meningkatkan aktifitas
melawan resistant gram-negative aerobes

Gram-positive Gram-negative marginal

Proteus mirabilis
Salmonella, Shigella
E. coli
H. influenzae
Enterobacter sp.
*Pseudomonas aeruginosa*
 Antipsuedomonal Penicillins:
Ureidopenicillins
(Piperacillin)
Dikembangkan utk meningkatkan aktifitas melawan
resistant gram-negative aerobes
Gram-positive Gram-negative
Viridans Strep Proteus mirabilis
Group Strep. Salmonella, Shigella
Enterococcus E. coli
L-H. influenzae
Anaerobes Enterobacter spp.
Fairly good activity *Pseudomonas aeruginosa*
including Bacteroides spp. Klebsiella spp.
-Lactamase Inhibitor Combos
(Unasyn, Augmentin, Zosyn)

Dikembangkan utk melawan aktifitas enzim -

lactamase yg dihasilkan mikroorganisme
Gram-positive Gram-negative
MSSA H. influenzae
E. coli
Anaerobes Proteus sp.
Bacteroides sp.Klebsiella sp.
Neisseria gonorrhoeae
Moraxella catarrhalis
Only ZOSYN covers Pseudomonas aeruginosa
 IV conversion to PO

• Penicillin to Penicillin
• Ampicillin to Amoxicillin
• Oxacillin to Dicloxacillin
 Anti-Staphlococcal
 Liquid tidak stabil
 Recommend cephalexin for PO Staphylococcal
treatment if can not swallow capsules
• Unasyn to Augmentin
Cephalosporins
 Cephalosporins by Generation
1st Generation 2nd Generation 3rd Generation 4th Generation

Cefadroxil 1 Cefaclor1 Cefdinir 1 Cefepime2

Cephalexin1 Cefprozil1 Cefixime1
Cefazolin Cefuroxime axetil1 Cefpodoxime1
Cefotetan3 Ceftibuten1
Cefoxitin3 Ceftazidime2
Cefuroxime Cefotaxime
sodium Ceftriaxone
Oral dosage form available
1
Anaerobe coverage
3

Antipseudomonal activity notable

2
 1st Generation Cephalosporins

Aktifitas paling baik melawan gram-

positive aerobes, aktifitas terbatas thdp
gram-negative aerobes

Gram-positive Gram-negative
MSSA E. coli
Pen-Susp S. pneumoniae K. pneumoniae
Group Streptococci P. mirabilis
Viridans Streptococci
 2nd Generation Cephalosporins

• Aktifitas lemah thdp gram-positive aerobes, ttpi

lebih aktif thdp gram-negative aerobes
• Aktifitas terhadap mikroorganisme anaerobes
Gram-positive Gram-negative
MSSA E. coli
Pen-susp S. pneumoniae K. pneumoniae
Group Streptococci P. mirabilis
Viridans Streptococci H. influenzae
M. catarrhalis
Neisseria spp.
 3rd Generation Cephalosporins
Spectrum of Activity

• Aktifitas lemah thdp gram-positive aerobes,

tttpi lebih kuat thdp gram-negative aerobes
• Ceftriaxone and cefotaxime memiliki aktifitas
paling baik against gram-positive aerobes,
meliputi PCN-resistant S. pneumoniae
3rd Generation Cephalosporins
Spectrum of Activity

Gram-negative aerobes
E. coli K. pneumoniae
P. mirabilis H. influenzae
M. catarrhalis N. gonorrhoeae
N. meningitidis
Citrobacter spp. Enterobacter spp.
Acinetobacter sp. Morganella morganii
Serratia marcescens Providential
Ceftazidime only: Pseudomonas aeruginosa
 4th Generation Cephalosporins
• Extended spectrum of activity
• Gram-positives: similar to ceftriaxone
• Gram-negatives: similar to ceftazidime
(including Pseudomonas aeruginosa), also
covers beta-lactamase producing Enterobacter
spp.
• Stabil thdp -lactamases
 IV to PO - Cephalosporins
• Cefazolin to Cephalexin
• Cefoxitin to Cefuroxime axetil + Metronidazole
• Ceftriaxone or Cefotaxime to Cefdinir or Cefixime
• Ceftazidime or Cefepime to: Treating Pseudomonas?

Yes- ciprofloxacin
No- cefdinir
Carbapenems
 Carbapenems
(Imipenem, Meropenem, Ertapenem)

• Aktivitas spektrum paling luas di antara semua

antimikroba: gram-positive & gram-negative
aerobes & anaerobes
• Meropenem and Imipenem cover P. aeruginosa
• Ertapenem does NOT cover P. aeruginosa
• Bacteria not covered by carbapenems:
Staph. epidermidis
C. difficile
Monobactams
 Monobactams
(Aztreonam)

Gram-negatives
E. coli K. pneumoniae
P. mirabilisS. marcescens
H. influenzae M. catarrhalis
Enterobacter Citrobacter
Providencia Morganella
Salmonella Shigella
Pseudomonas aeruginosa

No activity against gram-positives or

anaerobes
 -Lactams
ADME
• Absorption
 PO forms have variable absorption
 Food can delay rate and extent of absorption
• Distribution
 Widely to tissues & fluids
 CSF penetration:
Parenteral PCNs – limited unless inflamed meninges
Parenteral 3rd & 4th gen cephalosporins, meropenem, &
aztreonam – penetrate well
• Metabolism & Excretion
 Primarily renal elminiation
 Nafcillin, oxacillin, ceftriaxone, cefoperazone: via liver
 ALL -lactams have short elimination half-lives
 -Lactams
Adverse Effects
Hypersensitivity – 0.4% to 10 %
 Mildto severe: rash to anaphylaxis & death
 Cross-reactivity exists among all penicillins
and even other -lactams (5 to 10%)
 Desensitization is possible
 Aztreonam does not display cross-
reactivity with penicillins and can be
used in penicillin-allergic patients
 -Lactams
Adverse Effects
• Neurologic: notably high dose PCN & carbapenems
• Increased incidence w/ high doses &/or renal
insufficiency
• Irritability, jerking, confusion, seizures
• Hematologic
• Leukopenia, neutropenia, thrombocytopenia with
prolonged therapy (> 2 weeks)
• Gastrointestinal
• Increased LFTs, nausea, vomiting, diarrhea,
pseudomembranous colitis
• Interstitial Nephritis (Type IV hypersensitivity reaction)
• Especially with nafcillin
Fluoroquinolones
 Fluoroquinolones
(Ciprofloxacin, Levofloxacin, Moxifloxacin)
• Antibiotik sintetis baru dikembangkan sebagai
respons terhadap resistensi yang berkembang
• Spektrum aktivitas yang luas
• Kerugian: munculnya resistensi
 Improved PK properties – excellent
bioavailability, tissue penetration,
prolonged half-lives
• Concentration-dependent bactericidal
activity
 Fluoroquinolones
Mechanism of Action
• Menghambat topoisomerases bakteri yang diperlukan
untuk sintesis DNA
• Topoisomerase IV – Primary target for gram-positives
• Resistance
• Altered target sites: Paling penting dan paling umum
• Altered cell wall permeability
• Efflux pumps
• Cross-resistance occurs between FQs
• DNA gyrase – Primary target for gram-
negatives
 Fluoroquinolones
Spectrum of Activity
• Gram-positive: moxi>levo>>cipro
 MSSA
 Streptococcus pneumoniae
• Gram-Negative: cipro=levo>moxi
 Enterobacteriaceae
 H. influenzae, M. catarrhalis, Neisseria sp.
 Pseudomonas aeruginosa –ciprofloxacin &

levofloxacin
• Atypical bacteria: all have excellent activity
 Fluoroquinolones
ADME

• Absorption: bioavailabilitas yang baik

• Makanan menunda konsentrasi puncak
• Distribution: distribusi jaringan yang luas
• Lung, skin/soft tissue, bone, urinary tract (not
moxifloxacin)
• Minimal CSF penetration
• Metabolism & Elimination – renal and hepatic
• Exception: Moxifloxacin is NOT reanally
eliminated
 Fluoroquinolones
Adverse Effects
• Gastrointestinal: nausea, vomiting, diarrhea
• CNS: headache, agitation, insomnia, Pusing,
hallucinations
• Cardiac:
• Assumed to be class effect
• Led to withdrawal of grepafloxacin, sparfloxacin
• Articular Damage: cartilage damage, arthralgia
• Dysglycemias
• Led to withdrawal of gatifloxacin
• Hepatotoxicity
• Led to withdrawal of trovafloxacin
 Fluoroquinolones
Drug Interactions

• Divalent and trivalent kation

• Zinc, Iron, Calcium, Aluminum, Magnesium
• Antacids, Sucralfate, enteral feeds
• Administer doses 2 to 4 hours apart; FQ first
Macrolides
 Macrolides
Mechanism of Action
• Menghambat sintesis protein dengan
mengikat secara reversibel ke subunit
ribosomal 50S
 Bacteriostatic
 Time-dependent activity
• Resistance
 Effluxpumps
 Altered target sites
 Cross-resistance occurs between all macrolides
 Macrolides
(Erythromycin, Azithromycin, Clarithromycin)
• Erythromycin: narrow spectrum of
activity, short t1/2, not acid labile, GI
intolerance
• Clarithromycin & azithromycin:
 Broader spectrum of activity
 Improved PK properties:
 Better bioavailability
 Better tissue penetration
 Prolonged half-lives
 Improved tolerability
 Macrolides
Spectrum of Activity

• Gram-Positive Aerobes: Clarithr>Erythr>Azithr

 MSSA
 S. pneumoniae: resistance is emerging
 Group and viridans streptococci
• Gram-Negative Aerobes: Azithr>Clarithr>Erythr
• H. influenzae, M. catarrhalis, Neisseria sp.
• NO activity against any Enterobacteriaceae
• Anaerobes: upper airway anaerobes
• Atypical Bacteria
• Other Bacteria: Mycobacterium avium complex
 Macrolides
ADME
• Absorption
 Erythromycin: variable absorption of 15% - 45%
 Clarithromycin: 55%
 Azithromycin: 38%
• Distribution
 Clarithromycin & azithromycin extensive tissue
penetration with minimal CSF penetration
• Metabolism & Elimination
 Clarithromycin partially eliminated by the kidney
 ALL hepatic elimination
 t1/2: erythro 1.4 hr, clarithro 3-7 hr, azithr 68 hr
 Macrolides
Adverse Effects

• Gastrointestinal: up to 33 %
 Nausea, vomiting, diarrhea, dyspepsia
 Erythro > > clarithro, azithro

• Thrombophlebitis: IV Erythro & Azithro

• Ventricular arrhythmias
• Other: ototoxicity (high dose erythro in
patients with RI)
 Macrolides
Drug Interactions
• Erythromycin and Clarithromycin are
STRONG INHIBITORS of cytochrome p450
system (3A4):
Digoxin
Carbamazepine Valproic acid
Benzodiazepines Methylprednisolone
Phenytoin Warfarin
Ergot alkaloids Azole antifungals
Tacrolimus Cyclosporine
Sirolimus Calcium Channel Blockers
Aminoglycosides
 Aminoglycosides
Mechanism of Action
• Penghambatan sintesis protein dengan mengikat ribosome
30S secara ireversibel yang mengakibatkan membran sel
bakteri rusak
 Concentration-dependent killer
• Resistance
 Alteration
of ribosomal binding site
 Decreased intracellular penetration

• Bactericidal
 Aminoglycosides
Spectrum of Activity
• Gram-Negative Aerobes
E. coli, K. pneumoniae, Proteus sp.
Acinetobacter, Citrobacter, Enterobacter sp.
Morganella, Providencia, Serratia, Salmonella, Shigella
Pseudomonas aeruginosa (amik>tobra>gent)

• Gram-Positive Aerobes (in combination w/ cell

wall inhibitor)
S. aureus and coagulase-negative staph
viridans streptococci
Enterococcus sp. (gentamicin)
 Aminoglycosides
Pharmacology

• Absorption: negligible
• Distribution
 Hydrophilic: widely distributes into body fluids
but NOT the CSF
 Distribute poorly into adipose tissue

• Elimination
 85-95% eliminated unchanged via kidney
 t1/2 dependent on renal function
 Aminoglycosides
Adverse Effects
• Nephrotoxicity
 Direct proximal tubular damage - reversible if caught
early
 Risk factors: High troughs, prolonged duration of
therapy, underlying renal dysfunction, concomitant
nephrotoxins
• Ototoxicity
 8th cranial nerve damage – irreversible vestibular and
auditory toxicity
 Vestibular: dizziness, vertigo, ataxia
 Auditory: tinnitus, decreased hearing
 Risk factors: same as for nephrotoxicity
Vancomycin
 Vancomycin
Mechanism of Action

• Inhibits bacterial cell wall synthesis at

final stage of peptidoglycan polymers
• Bactericidal (except for Enterococcus)
• Time dependent killer
• Resistance
• Modification of D-alanyl-D-alanine binding site
of peptidoglycan
 Vancomycin
Spectrum of Activity
• Gram-positive bacteria
 MSSA, MRSA and S. epidermidis
 Streptococcus pneumoniae (including PRSP),
viridans streptococcus, Group streptococcus
 Enterococcus
 Corynebacterium, Bacillus, Listeria, Actinomyces

• Anaerobes
 Clostridium
sp. (including C. difficile),
Peptostreptococcus, Peptococcus

No activity against gram-negative aerobes

 Vancomycin
ADME
• Absorption
• oral is negligible
• IV terapi yang diperlukan untuk infeksi sistemik
• Distribution
 Distributes widely into body tissues and fluids,
including adipose tissue
 Variable penetration into CSF, even with inflamed
meninges
• Elimination
 Primarily eliminated unchanged by the kidney
 Vancomycin
Adverse Effects

• Red-Man Syndrome
 Erythema multiforme-like reaction with intense
pruritus, tachycardia, hypotension, rash
involving face, neck, upper trunk, back and
upper arms
 Related to infusion rate
 Resolves spontaneously after discontinuation
 Lengthen infusion (over 2 - 3 hr) and/or pretreat
with antihistamines
• Hematologic: neutropenia, eosinophilia
 Vancomycin
Clinical Uses

Serious gram-positive infections

(MRSA) in -lactam allergic
patients
Oxazolidinone
 Linezolid
Mechanism of Action

• Inhibits bacterial protein synthesis by

binding to bacterial 23S ribosomal RNA
of the 50S subunit
• Time dependent killer
• Bacteriostatic against enterococci &
staphylococcus
• Bacteriocidal against streptococci
• Resistance: RARE
• Alterations in ribosomal binding sites
 Linezolid
Spectrum of Activity

• Gram-Positive Bacteria
 MSSA, MRSA and S. epidermidis
 Streptococcus pneumoniae (including
PRSP), viridans streptococcus, Group
streptococcus
 Enterococcus faecium & faecalis (including
VRE)
 Bacillus, Listeria, Clostridium sp. (NOT C.
difficile), Peptostreptococcus, P. acnes
 Linezolid
ADME
• Absorption: 100% bioavailable
• Distribution: readily distributes into well-
perfused tissue; CSF 30%
• Metabolism & Elimination: primarily
metabolized via liver; 30% parent drug
excreted via kidney
 Linezolid
Adverse Effects

• Gastrointestinal: nausea, vomiting,

diarrhea (11%)
• Headache: 10%
• Thrombocytopenia: 3 to 10%
 Overall myelosuppression often with
treatment durations of >2 weeks
 Therapy should be discontinued and
hematologic counts will return to normal
 Linezolid
(Drug-Drug & Drug-Food Interactions)

• Linezolid is a reversible, nonselective

monoamine oxidase inhibitor
• Sindrom serotonin dimungkinkan dengan
penggunaan bersamaan:
 Tyramine rich foods
 Serotonergic medications (SSRIs, MAOIs)
• Foods high in tyramine:
 Aged, fermented, pickled, smoked
 Cheese, pepperoni, soy sauce, red wines, beer,
sauerkraut
 Serotonin Syndrome
Presence of three or more of the following:
• Agitation (34%)
• Abdominal pain (4%)
• Ataxia/incoordination (40%)
• Diaphoresis (45%)
• Diarrhea (8%)
• Hyperpyrexia (45%)
• Hypertension/hypotension (35%)
• Hyperthermia
• Hyper-reflexia (52%)
• Mental status change
Daptomycin
 Daptomycin
Mechanism of Action

• Mengikat membran bakteri dan menyebabkan

depolarisasi cepat dari potensi membran,
menghambat sintesis protein, DNA, RNA dan
protein
 Concentration-dependent
 Bactericidal activity
• Mechanism of Resistance
 Currently, no mechanisms of resistance have been
identified
 Daptomycin
Spectrum of Activity

• Gram-Positive Bacteria
 MSSA, MRSA and Staph. epidermidis
 Streptococcus pneumoniae (including PRSP),
viridans streptococcus, Group streptococcus
 Enterococcus faecium AND faecalis (including
VRE)

• Gram-Negative Aerobes: inactive

 Daptomycin
ADME

• Absorption: minimal
• Distribution: PP= 95%, small volume of
distribution
 NOT indicated for TREATMENT of PNEUMONIA
• Metabolism & Elimination: kemungkinan
metabolisme ginjal dan 80% obat induk
diekskresikan melalui ginjal
 Daptomycin
• Adverse Effects
 Gastrointestinal: nausea, diarrhea,
constipation
 Headache, insomnia
 Injection site reactions
 Rash
 Myopathy and CPK elevations

• Drug Interactions
 HMG-CoA reductase Inhibitors (statins)
Clindamycin
 Clindamycin
Mechanism of Action

• Membalikkan mengikat subunit ribosomal 50S

menghambat sintesis protein bakteri
• Bacteriostatic or bactericidal depending on drug
concentration, infection site, and organism
• Binds in close proximity to macrolides –
competitive inhibition
• Resistance
• Altered binding site: confers resistance to
clindamycin & macrolides
 Clindamycin
Spectrum of Activity
• Gram-Positive Aerobes
• MSSA
• CA MRSA
• Streptococcus pneumoniae (only PSSP) - resistance is
developing
• Group and viridans streptococci
• Anaerobes
• Bacteroides sp
• Peptostreptococcus
• Actinomyces
• Propionibacterium
• Clostridium sp. (not C. difficile)
 Clindamycin
ADME

• Absorption: Rapidly & completely absorbed

(90%); food with minimal effect on
absorption
• Distribution
• High concentrations in bone and urine
• NO significant levels in CSF
• Metabolism & Elimination
 Clindamycinprimarily metabolized by the liver
 10% of an oral dose excreted in urine
 Clindamycin
Adverse Effects
• Gastrointestinal: >10%
 Nausea, vomiting, diarrhea, dyspepsia
 Esophagitis
 Pseudomembranous colitis
 Mild to severe diarrhea
 Requires treatment with metronidazole
• Hepatotoxicity: rare
 Elevated transaminases
• Allergy: rare
Metronidazole
 Metronidazole
Mechanism of Action

• After complex reduction reactions,

causes DNA to lose helical structure and
results in inhibition of protein synthesis
• Concentration-dependent killer
• Bactericidal activity
• Resistance: relatively uncommon
 Impaired oxygen scavenging ability
 Altered ferredoxin levels
 Metronidazole
Spectrum of Activity

• Gram positive and negative anaerobes

 Bacteroides sp.
 Fusobacterium
 Prevotella sp.
 Helicobacter pylori
 Clostridium sp.
(Drug of choice: C. difficile pseudomembranous colitis)
• Anaerobic Protozoa
 Trichomonas vaginalis
 Giardia lamblia
 Gardnerella vaginalis
 Metronidazole
ADME

• Absorption: Rapidly and completely (90%)

• Distribution
 Saliva,bile, seminal fluid, bone, liver, abscesses,
lung and vaginal secretions
 Penetrates CSF

• Metabolism & Elimination

 30% - 60% metabolized by the liver
 Kidney excretes up to 77% as unchanged drug
 Urine may be dark or reddish-brown
 Metronidazole
Adverse Effects

• Gastrointestinal: Nausea, vomiting,

stomatitis, metallic taste
• CNS: seizures, encephalopathy,
confusion, headache
 Requires discontinuation of metronidazole
• Neuromuscular & skeletal: Peripheral
neuropathy
 Metronidazole
Drug Interactions

Drug Interaction
Warfarin  anticoagulant effect
Alcohol Disulfiram-like reaction
Phenytoin  phenytoin concentrations
Lithium  lithium concentrations
Phenobarbital  metronidazole concentrations
Rifampin  metronidazole concentrations
 Trimethoprim-
Sulfamethoxazole
(Bactrim)
 Bactrim
(Mechanism of Action)
• Provide sequential inhibition of folinic acid
synthesis; necessary for microbial DNA production
 SMX: Inhibits dihydropteroate synthase – inhibits
incorporation of p-aminobenzoic acid (PABA) into
dihydrofolic acid
 TMP: Inhibits dihydrofolate reductase – prevents
reduction of dihydrofolate to tetrahydrofolate
 Each agent is bacteriostatic, however, combination
displays bactericidal activity
• Resistance
 Mediated by point mutations in dihydro-pteroate
synthase and/or altered production or sensitivity of
dihydrofolate reductase
 Bactrim
(Spectrum of Activity)
• Gram-Positives:
 Some S. pneumoniae
 CA MRSA
 Staph aureus
 S. pyogenes
 Nocardia
• Gram-Negatives: Other:
 E. coli Pneumocystis jiroveci (carinii)
 K. pneumoniae
 Salmonella, Shigella
 M. catarrhalis
 Haemophilus sp.
 N. gonorrhoeae
 Stenotrophomonas maltophilia
 Bactrim
ADME
• Absorption: Rapidly & completely absorbed (>
90%)
 Peaks are higher and more predictable with IV
administration
• Distribution: urine, joints, sputum, middle ear
fluid, bile and CSF
• Metabolism & Elimination:
• SMX- extensive metabolized in liver and 10%-30%
parent drug excreted in urine
• TMP- metabolized by liver and up to 75% parent drug
excreted in urine
 Bactrim
Adverse Effects
• Gastrointestinal: Nausea, vomiting, diarrhea
• Hematologic
 Leukopenia, thrombocytopenia, eosinophilia
 Hemolysis (with G-6-PD deficiency)
• Dermatologic: Rash, urticaria, epidermal
necrolysis, Steven’s-Johnson, drug fever
• CNS: Headache, seizures, KENICTERUS in
neonates
• Other: phlebitis