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Classification of Bacteria

Coagulase +
Catalase +
Coagulase -
Aerobic
COCCI

GM +ve
Alpha-hemolysis
Blue to purple
Anaerobic
Catalase - ß-hemolysis

Non-hemolytic
Aerobic
BACILLI
Anaerobic

COCCI
GM -ve
Fasitidious
Pink to red Glocuse
Aerobic
fermenters
BACILLI Rapid growth
Anaerobic Non-fermenters
Bacteria

Gram stain

Gm varibal
(Atypical)
No stain
(Colourless)

Mycobacterium species
No stain
Acid fast stain
(Colourless)

Yusuf Muhammad Garwan, PharmD intern – IAU (2019)

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Staphylococcus Coagulase + S.aureus
Catalase +
Clusters

Coagulase -
Aerobic S.saprophyticus

S.epidermidis

COCCI
Viridans Strept
Alpha-hemolysis
S.pneumoniae

S. pyogens
Streptococcus ß-hemolysis
Catalase - S.agalactiae
Pairs/Chains
E. faecium
Non-hemolytic Enterococcus
E.faecalis

Preptococcus
Anaerobic
Preptostrptococcus

GM +ve

Corynebacterium
diphtheriae

Aerobic LISTERIA
MONOCYTOGENES

Bacillus anthracis

Bacilli

Propionibacterium

Lactobacillus C. perfringens

Anaerobic Actinomyces C. tetani

C. difficile
Clostridium
C. botulinum

Yusuf Muhammad Garwan, PharmD intern – IAU (2019)

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N.meningitides
Neisseria
COCCI N.gonorrhoae
Moraxella
catarrhalis

H. pylori

Campylobacter H.influenzae

Haemophilus H.Ducreyi
Fasitidious
Bordetella pertussis H.aegyptius

Brucella spp

Bartonella

GM -ve
E. coli

Klebsiella
Aerobic Aeromonas
Serratia
Glocose fermenters Vibrio cholera
Enterobacter
Enterobacteriacea
Citrobacter
Bacilli
Proteus
Rapid growth
Salmonella

Shigella

Bacteroides Pseudomonas
fragilis
Acinetobacter
Anaerobic Fusobacterium
Non-fermenters
Stenotrophomanas
Prevotella

Burkholderia

Yusuf Muhammad Garwan, PharmD intern – IAU (2019)

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C. trachomatis

Chlamydia C. pneumoniae

C. psittaci

M. pneumoniae

M. genitalium
Mycoplasma
M. hominis

M. urealyticum
Gm varibal
(Atypical)
R. rickettsii
Rickettsia
R. prowazekii

Treponema T. pallidum

Spirochetes Borrelia

Legionella pneumophila Leptospira

Gardenella vaginalis

M. tuberculosis

M. leprae

Mycobacterium species
Acid fast stain M. bovis

M. avium

Yusuf Muhammad Garwan, PharmD intern – IAU (2019)

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Classification of Antibiotics
Cell wall synthesis inhibitors (All are Bactericide)
1- Beta lactam
MoA: All beta-lactams inhibit cross-linking of peptidoglycan in the cell wall, leading to autolysis and cell death.
A- penicillins
Class/Drug/Route Spectrum of activity Side effect
Natural penicillin: Gm +ve: streptococcus, 1. Hypersensitivity reaction (ranging
Penicillin G (IV) C. perfringens, enterococcus faecalis, from mild rashes to drug fever to acute
Penicillin V (po) anaerobes interstitial nephritis to anaphylaxis).
Benzathine penicillin 2. Seizures (very high doses).
(IM) Gm -ve: N.Meningitides All beta lactam can cause 1 & 2.
3. Jarisch-Herxheimer reaction following
Atypical: Spirochetes (Treponema pallidum) the treatment of syphilis.
4. Anemia.
Extended spectrum Gm +ve: Streptococcus, Enterococcus Similar to those above, with a possibly
penicillin: faecalis, Listeria (ampicillin) higher incidence of diarrhea when given
Amoxicillin (po) orally (more with ampicillin).
Ampicillin (IV, used po to Gm -ve: Enteric GNRs (Except Klebsiella), H.
treat GI infections) pylori, H. influenza
Antipseudomonal Gm +ve: Streptococcus, Enterococcus Similar to those above.
penicillin: faecalis
Ticarcillin (IV)
Piperacillin (IV) Gm -ve: Enteric GNRs, H. influenza,
Carbenicillin (po) P. aeruginosa
Penicillin/Beta- As above +
Lactamase Inhibitor: MSSA
Amoxicillin/clavulanate P. aeruginosa (Tazosin)
(Augmentin) (PO & IV) Anaerobes
Piperacillin/tazobactam Acinetobacter (Ampicillin/sulbactam)
(Tazocin) (IV) Moraxella catarrhalis
Ampicillin/sulbactam Note:
(IV) • Tazocin: Does not cross BBB, should not be used in CNS infections.
• Augmentin: The dose of clavulanate is fixed in all oral dosage forms (125 mg),
overdose can cause serious complications (hepatotoxicity, diarrhea).
B-lactamase resistant Gm +ve: Streptococcus, MSSA (1st line). • Similar to those above, with a
penicillin: possibly higher incidence of acute
Methicillin (IV) interstitial nephritis.
Oxacillin (IV) • Phlebitis.
Nafcillin (IV)
Cloxacillin (po) Note:
Dicloxacillin (po) Nafacillin: hepatic elimination, no need for renal dose adjustment
B- Cephalosporins
Classified into 5 generations based on spectrum of activity:
Class/Drug/Route Spectrum of activity Side effect
1st generation: Gm +ve: MSSA, streptococcus 1. Hypersensitivity reactions.
Cephalexin (po) 2. Nephrotoxicity.
Cefadroxil (po) Gm -ve: some enteric GNRs 3. Diarrhea.
Cefazolin (IV) Note:
Yusuf Muhammad Garwan, PharmD intern – IAU (2019)

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• Does not cross BBB, should not be used in CNS infections.
• Surgical prophylaxis.
• 2nd line MSSA.
2nd generation: Gm +ve: MSSA, streptococcus Similar to those above.
Cefaclor (po) Gm -ve: H. influenza, Neisseria, some
Cefuroxime (IV & po) enteric GNRs

Cephamycins gp They are grouped with the 2nd generation Similar to those above.
Cefotetan (IV) because they have similar activity. Also, they
Cefoxitin (IV) are active against anaerobic Gm -ve.
Note:
• Does not cross BBB, should not be used in CNS infections.
• DDI: Cephalosporins with N-methylthiotetrazole (MTT) side chain (cefotetan) can
inhibit vitamin K production and prolong bleeding. Also, they can cause a
disulfiram-like reaction when coadministered with ethanol.
3rd generation: Gm +ve: MSSA and streptococci (except Similar to those above.
Cefixime (po) ceftazidime)
Ceftriaxone (IV,IM) Strong association with CDAD.
ceftazidime (IV.IM) Gm -ve: Neisseria, enteric GNRs,
Cefotaxime (IV,IM) P.aeruginosa (Ceftazidime) Cefpodoxime has the MTT side chain that
Cefpodoxime (po) Moraxella catarrhalis (ceftriaxone, can inhibit vitamin K production.
cefotaxime)
H. influenza (ceftriaxone)
Note:
Ceftriaxone:
• Once daily dosing.
• Hepatic elimination, no need for renal dose adjustment.
• Contraindicated in neonates due to possibly biliary sludging with resultant
hyperbilirubinemia. Cefotaxime is a safer alternative.
• DDI: interacts with calcium-containing medications to form crystals that can
precipitate in the lungs and kidneys.
4th generation: Gm +ve: MSSA and streptococci Similar to those above.
Cefepime (IV)
Cefpirome (IV) Gm -ve: enteric GNRs, p.aeruginosa 1. Neurotoxicity
2. Positive coombs test.
Note:
• The broadest-spectrum cephalosporin.
• Good empiric choice for many nosocomial infections.
5th generation: Gm +ve: MSSA, MRSA, streptococci, E. Similar to those above.
Ceftaroline (IV) faecalis
Ceftobiprole (IV) Gm -ve: Enteric GNRs, p. aeruginosa
(Ceftobiprole)
Cephalosporin/Beta- Gm +ve: strepto (ceftolozane/tazobactam) Similar to those above.
Lactamase Inhibitor:
Ceftazidime/avibactam Gm -ve: ESBL-producing GNRs, Resistance
Ceftolozane/tazobactam strains of p. aeruginosa
(IV) Note:
Ceftazidime/avibactam: active against a wide range of B-lactamases (ESBL, AmpC, KPC).
Ceftolozane/tazobactam: potent activity against MDR P. aeruginosa.

Yusuf Muhammad Garwan, PharmD intern – IAU (2019)

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C- Carbapenems
Drug/Route Spectrum of activity Side effect
Imipenem + cilastatin(IV) Gm +ve: MSSA, streptococci, Enterococcus 1. N/V.
Meropenem (IV) 2. Hypersensitivity reactions.
Doripenem (IV) Gm -ve: ESBL-producing GNRs, p. 3. Seizures (imipenem has a higher
Ertapenem (IM & IV) aeruginosa, Acinetobacter, anaerobes propensity). Minimize the risk by renal
dose adjustment and avoiding use in
patients with meningitis.
Note:
o Good empiric choice for many nosocomial infections.
Carbapenem/B- o Ertapenem:
lactamase inhibitor: • DOC for ESBL.
Meropenem- • Once daily dosing.
vaborbactam (IV) • Can be administered as IM.
• Has slightly less spectrum (not effective against P. aeruginosa, Acinetobacter,
and Enterococcus).
• Meropenem-vaborbactam: active against AmpC, and KPC strains.
D- Monobactams
Drug/Route Spectrum of activity Side effect
Aztreonam (IM & IV) Gm -ve: P. aeruginosa, most GNRs, Similar to those of other beta-lactams,
but with a low incidence of
hypersensitivity.
Note: It seems to be safe to administer to patients with allergies to other beta-lactams,
EXCEPT patients who have a specific allergy to ceftazidime.

2- Glycoprotein
MoA:
Bind to terminal D-ala-D-ala chains on peptidoglycan in the cell well, preventing further elongation of peptidoglycan
chains.
Telavancin, Dalbavancin, and Oritavancin also interfere with the cell membrane, disrupting membrane function.
Short-Acting Glycopeptides
Drug/Route Spectrum of activity Side effect
Vancomycin (IV) Gm +ve: MSSA, MRSA, streptococci, 1. Thrombophlebitis.
enterococcus faecalis, Clostridium difficile, 2. Ototoxicity (dose-dependent).
preptococcus 3. Nephrotoxicity.
4. Hypokalemia.
5. Thrombocytopenia.
6. Red man syndrome (with rapid IV
infusion).
Teicoplanin (IV & IM) Lower toxicity, higher penetration (more
lipophilicity), no red man syndrome,
longer half live.
Telavancin (IV) Lipoglycopeptides with improved activity Similar to those above.
against MRSA that is less susceptible to
vancomycin. taste disturbances and foamy urine.
Note:
Vancomycin:
• Has slow onset of action (24 h).
• Not active against listeria.
• Used orally for C. difficile.
Yusuf Muhammad Garwan, PharmD intern – IAU (2019)

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Long-Acting Glycopeptides
Drug/Route Drug/Route Drug/Route
Dalbavancin (IV) Gm +ve: MSSA, MRSA, streptococci, 1. N/V, diarrhea
Oritavancin (IV) enterococcus faecalis 2. Rash

Oritavancin:
• Infusion-related reactions: if it is
infused quickly, so it is given over 3
hours.
Note:
• Approved for skin and subcutaneous tissue infections as single dose (half-life >
week).
• DDI: Inhibits warfarin metabolism and may increase the risk of bleeding when given
with it.

3- Miscellaneous group
MoA of Fosfomycin: inhibits bacterial cell wall synthesis via preventing the production of the building blocks
of peptidoglycan.
Drug/Route Spectrum of activity Side effect
Fosfomycin (po) Gm +ve: S. saprophyticus, enterococci 1. Painful or difficult urination.
2. N/V, diarrhea.
Gm -ve: Enteric GNR (ESBL, CRE strains),
Pseudomonas
• Used in uncomplicated UTI as a single dose.
• IV formulations are available in some countries.
Bacitracin (topical) Gm -ve & Gm +ve 1. Serious nephrotoxicity (if used IV).
2. Hypersensitivity (topical application).

Cell membrane function inhibitors (All are Bactericide)


Polymyxin
MoA: Bind to the outer membrane of Gram-negative bacteria, leading to disruption of membrane stability and
leakage of cellular contents.
Polymyxin E (Colistin) (IV) Gm-ve: many GNRs (including MDR A. 1. Nephrotoxicity (common)
Polymyxin B (IV, IM) baumannii, P. aeruginosa, and K. 2. Neurotoxicity: dizziness, weakness,
pneumoniae), Stenotrophomonas paresthesias, or mental status
maltophilia changes.
3. Neuromuscular blockade >>
respiratory arrest.
Note:
o Lack of activity against Portus, Providencia, Serratia, and Anaerobes. Should not be
used alone for empirical therapy.
o Polymyxin B: is recommended for routine systemic use in invasive infections, due to
superior PK characteristics, simpler dosing, and lower risk of nephrotoxicity.
o Colistin: recommend for lower UTI, because the conversion of colistimethate
(prodrug) to the active moiety colistin occurs in the urinary tract.
o Inhaled colistin: can be used in conjunction with IV therapy for XDR gram-negative
HAP or VAP.
o Intrathecal/Intraventricular therapy: can be used in conjunction with IV therapy for
ventriculitis or meningitis caused by MDR and XDR gram-negative pathogens.

Yusuf Muhammad Garwan, PharmD intern – IAU (2019)

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Cyclic Lipopeptides
Daptomycin (Cubicin) (IV) Gm+ve: MSSA, MRSA, VRSA, streptococci, 1. Rhabdomyolysis
enterococci (VRE) 2. Myalgia
3. Eosinophilic pneumonia
Note:
Contraindicated in pulmonary infections (inactivated by lung surfactant)

Protein synthesis inhibitors (All are Bacteriostatic except Aminoglycoside)


1- 30 subunit
A- Aminoglycoside

MoA: Bind to the bacterial ribosome (the 30S subunit), causing misreading of the genetic code, leading to incorrect
protein formation and interruption of protein synthesis.
Drug/Route Spectrum of activity Side effect
Gentamicin (IV) Gm +ve (in combination with beta-lactam 1. Ototoxicity (deafness, irreversible).
Amikacin (IV) or glycopeptide): MSSA, MRSA, viridian 2. Nephrotoxicity.
Tobramycin (IV) streptococcus, enterococcus 3. Neuromuscular blockade > respiratory
Streptomycin (IV) paralysis
Neomycin (PO & Topical) Gm -ve: Enteric GNR, H. influenza, P.
aeruginosa (amikacin, tobramycin, (Time dependent SE)
gentamicin), Acinetobacter (amikacin)

Acid fast: TB (streptomycin)


Plazomicin (IV) Gm +ve: MSSA, MRSA 1. Nephrotoxicity.
2. Ototoxicity.
Gm -ve: Enteric GNR 3. Neuromuscular blockade.
4. Fetal harm in pregnant mothers.
Plazomicin is approved for complicated UTI.
B- Tetracycline & Glycylcyclines
MoA: bind to the bacterial ribosome at the 30S subunit, preventing the docking of transfer RNA carrying new amino
acids for addition to the elongating protein chain.
Drug/Route Spectrum of activity Side effect
Doxycycline (IV, PO) Gm +ve: MSSA, MRSA, S. pneumoniae 1. Esophageal irritation.
Minocycline (IV, PO) 2. Photosensitivity.
Tetracycline (PO) Gm -ve: H. pylori 3. Vestibular dysfunction (Balance
Demeclocycline (PO) disorder).
Atypical: mycoplasma, chlamydia, 4. Renal toxicity from date expired
Glycylcyclines: rickettsia, spirochetes (Borrelia burgdorferi) tetracycline.
Tigecycline (IV) Plasmodium species (malaria) 5. Deposition in the bone and teeth
(permanent).
Flurocycline: Tigecycline: 6. Severe N/V, diarrhea (Tigecycline).
Eravacycline (IV) As above +
Enterococcus (including VRE)
Aminomethylcycline: Gm -ve: Most GNR (ESBL)
Omadacycline (PO, IV) Anaerobes
Acinetobacter
Tigecycline:
• Lack of activity against pseudomonas, Portus, and Providencia
• Contraindicated in bacteremia (distributed to the tissues)
• Hepatic elimination, no need for renal dose adjustment
Yusuf Muhammad Garwan, PharmD intern – IAU (2019)

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2- 50 subunit
A- Macrolides & Ketolide
MoA: Bind to the 50S subunit of bacterial ribosomes, preventing the ribosomes from shuffling along and adding a
new amino acid to the elongating protein chain
Drug/Route Spectrum of activity Side effect
Erythromycin (PO) Gm +ve: S. pneumoniae, S. pyogenes, C. 1. N/V, diarrhea (more with
Clarithromycin (PO) Diphtheria erythromycin)
Azithromycin (PO & IV) 2. Hepatotoxicity
Gm -ve: H. influenzae, Moraxella catarrhalis, 3. Prolongation of the QT interval (more
Ketolide: H. pylori with erythromycin)>> rare
Telithromycin (PO)
Acid fast: Mycobacterium avium Complex
(MAC)

Atypical: mycoplasma, chlamydia,


rickettsia, spirochetes
Note:
• Telithromycin has better activity against resistant S. pneumoniae. Approved for
CAP.
• DDI: These drugs (with the exception of azithromycin) are potent inhibitors of drug-
metabolizing cytochrome P450 enzymes
• Azithromycin: hepatic elimination, no need for renal dose adjustment.
• Has anti-inflammatory effect, may add benefit in COPD exacerbation.

Fidaxomicin (PO) Gm +ve: C. difficile Most of the adverse effects reported in


clinical trials are associated with C.
difficile infection, including nausea,
diarrhea, abdominal pain, and cramping.
Approved for C. diffi diarrhea

B- Chloramphenicol
Drug Spectrum of activity Side effect
Chloramphenicol (IV) Broad spectrum against Gm -ve & Gm +ve 1. Bone marrow suppression (70% of
(MRSA) cases are aplastic anemia).
2. Loss of vision.
3. Gray baby syndrome occurs in
newborn infants:
− Due to accumulation of toxic
metabolites of chloramphenicol.
− Vomiting, Hypotension, cyanosis,
CVS collapse and death (40% of
patients within 2 days of symptoms)
4. Jarisch-Herxheimer reactions
following the treatment of syphilis
and typhoid fever.
Note:
Today it is not used anymore due to higher risk for toxicity and availability of
alternatives for MRSA.

Yusuf Muhammad Garwan, PharmD intern – IAU (2019)

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C- Lancosamide
MoA: Binds at a site on the 50S ribosome right next to where the macrolides bind and acts similarly in preventing
protein synthesis by preventing the ribosome from moving on to adding another amino acid in the
protein chain.
Drug Spectrum of activity Side effect
Clindamycin (PO,IV) Gm +ve: anaerobes, MSSA, community- 1. Diarrhea (up to 20%).
Lincomycin (IV) acquired MRSA, S. pyogenes 2. CDAD which is major concern that
may occur weeks after the drug is
Gm -ve: Anaerobes withdrawn.
3. Skin rash (10%).
Fungal: Pneumocystis jirovecii 4. Inhibits neuromuscular transmission
and potentiates skeletal muscle
Parasite: Plasmodium species (malaria), relaxants (atracurium) like
Toxoplasma aminoglycosides antibiotic.
Note:
• Has antitoxin effect, its recommended as an adjunct to B-lactams in severe invasive
S. pyogens infection.
• Hepatic elimination, no need for renal dose adjustment.
• Does not cross BBB, should not be used in CNS infections.
• Higher level of resistance among the Gram-negative anaerobes (such as Bacteroides
fragilis) than with metronidazole. Because of these limitations and clindamycin’s
tendency to cause GI toxicity, it is best used empirically for non-severe infections of
the skin and oral cavity, or as definitive therapy when susceptibilities are known.
D- Oxazolidinones
MoA: Bind to the 50S ribosomal subunit, blocking the formation of a stable 70S initiation complex and preventing
translation. This binding site is distinct from other protein synthesis inhibitors.
Drug Spectrum of activity Side effect
Linezolid (PO, IV) Gm +ve: MSSA, MRSA, VRE, streptococci 1. GI disturbance.
Tedizolid (PO, IV) (including MDR S. pneumoniae), enterococci 2. Bone marrow suppression
(including VRE), Nocardia (thrombocytopenia).
3. Peripheral neuropathy.
Acid fast: Mycobacterium tuberculosis 4. Lactic acidosis

(2&3 >> with long-term use >2 weeks)


Note:
• Oral alternative for MRSA.
• Hepatic elimination, no need for renal dose adjustment.
• Contraindicated in bacteremia (distributed to the tissues).
• Linezolid>> BID, Tedizolid>> OD
• DDI: Linezolid is an inhibitor of monoamine oxidase (MAO) and can cause serotonin
syndrome when given concurrently with serotonergic agents such as selective
serotonin reuptake inhibitors (SSRIs).
E- Streptogramins
MoA: bind to different sites on the 50S subunit of the bacterial ribosome to prevent bacterial protein synthesis.
Drug Spectrum of activity Side effect
quinupristin/dalfopristin Gm +ve: MSSA, MRSA, VRSA, streptococci, 1. Phlebitis, use central line.
combination (Synercid ) Enterococcus faecium (VRE) 2. Arthralgia and myalgia.
(IV)
DDI: Inhibits cytochrome P450 3A4, so clinicians need to be aware of potential drug
interactions.

Yusuf Muhammad Garwan, PharmD intern – IAU (2019)

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DNA synthesis inhibitors (All are Bactericide)
Fluoroquinolones
MoA: Inhibit DNA topoisomerases
Drug Spectrum of activity Side effect
1st generation (quinolones): Gm -ve: enteric GNR 1. CNS: dizziness, confusion, and
Nalidixic acid hallucinations (Elderly) or insomnia
(Younger patients).
2nd generation: Gm +ve: MSSA, S. Pneumonia 2. Peripheral neuropathy
Ciprofloxacin (PO, IV) (except ciprofloxacin) 3. Prolongation of the QT interval
Norfloxacin (PO) 4. Tendonitis.
Ofloxacin (PO) Gm -ve: Entering GNRs, H. influenza, 5. Tendon rupture (more common in the
p. aeruginosa (only cipro & levo) elderly, patients with renal
3rd generation: dysfunction, and those taking
Levofloxacin (PO, IV) Atypical: mycoplasma, chlamydia, corticosteroids)
legionella 6. Photosensitivity.
7. Hepatotoxicity.
Acid fast: TB (only levofloxacin) 8. Visual disturbance.
th
4 generation: As above + 9. Dysglycemia (more with
Moxifloxacin (PO, IV) moxifloxacin)
Gemifloxacin (PO) Anaerobes (only moxifloxacin)
Delafloxacin (PO, IV) TB (only moxifloxacin)
MRSA (only Delafloxacin)
Note:
o DDI: inhibits P450 enzyme and increases plasma levels of theophylline and warfarin.
o Levofloxacin, ciprofloxacin: oral alternatives for pseudomonas infections.
o Moxifloxacin:
• Hepatic elimination, no need for renal dose adjustment
• Not used for UTI due to poor penetration

Nitroimidazoles
MoA: Anaerobic bacteria and protozoa activate a part of the nitroimidazole molecule that forms free radicals, which
are thought to damage DNA and lead to cell death.
Drug Spectrum of activity Side effect
Metronidazole (PO, IV) Gm +ve & Gm -ve anaerobes: 1. N/V, diarrhea, Abdominal pain.
Tinidazole (PO) Bacteroides, Fusobacterium, and 2. Metallic taste in the mouth.
Clostridium species 3. Dark urine.
4. Headache, vertigo, dizziness,
Protozoa: Trichomonas, Entamoeba, insomnia.
and Giardia 5. Reversible peripheral neuropathy
(Dose-related)
Gm -ve: H.Pylori

Note:
o Lack activity against anaerobes that reside in the mouth (Preptostreptococcus,
Actinomyces, and Propionibacterium).
o Hepatic elimination, no need for renal dose adjustment.
o DDI:
• Inhibits metabolism of warfarin – bleeding.
• Disulfiram -like reaction with ethanol.
Yusuf Muhammad Garwan, PharmD intern – IAU (2019)

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Nitrofuran
Drug Spectrum of activity Side effect
Nitrofurantoin (PO) Gm +ve: S. saprophyticus, enterococci 1. N/V
2. Hemolytic anemia
Gm -ve: Enteric GNR (except Serratia) 3. Pulmonary toxicity:
• Acute pneumonitis manifesting as
cough, fever, and dyspnea. This form
typically resolves soon after drug
discontinuation.
• Chronic pulmonary fibrosis can
occur, most commonly with
prolonged nitrofurantoin therapy;
recovery of lung function is limited
after drug discontinuation.

Folic acid synthesis inhibitors (All are Bactericide)


Folate antagonist
Drug Spectrum of activity Side effect
Bactrim (trimethoprim- Gm +ve: MSSA, community acquired TMP/SMX:
sulfamethoxazole) (PO, IV) MRSA, S. pneumoniae, S. pyogenes, 1. Rash
Dapsone (PO, Topical) Listeria. 2. Thrombocytopenia (dose
Pyrimethamine dependent)
Sulfadiazine Gm -ve: H. influenzae, 3. Nephrotoxicity:
Sulfadoxine Stenotrophomonas maltophilia, • Crystalluria and AIN caused by the
enteric GNRs, Salmonella, SMX
Shigella, Nocardia, • Blockade of creatinine secretion by
TMP can cause an increase in Scr
Fungal: Pneumocystis jirovecii without a true decline in GFR.
(formerly known as P. carinii), 4. Hyperkalemia (dose dependent)

Parasite: Toxoplasma gondii


(pyrimethamine and sulfadiazine)

• DDI: TMP/SMX has a significant drug interaction with warfarin, leading to


higher-than-anticipated prothrombin times.
• Contraindication: G6PD deficiency.

Anti TB
Rifamycins
MoA: RNA synthesis inhibitors
Drug Spectrum of activity Side effect
Rifampin (rifampicin) (PO, IV) Acid fast: most mycobacteria 1. Hepatotoxicity.
Rifabutin 2. Orange discoloration of body fluid
Rifapentine Gm +ve: Staphylococcus such as urine, saliva and tears.
Rifaximin (not used for 3. DDI: Potent liver enzyme inducer
mycobacterial disease) Gm -ve: Acinetobacter, (CYTp450)
Enterobacteriaceae − Increases degradation of Warfarin,
Ant-diabetic Agents & Estrogens.

Yusuf Muhammad Garwan, PharmD intern – IAU (2019)

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o Rifampin is a drug of choice for tuberculosis, while rifabutin is a drug of choice
for mycobacterium avium complex (MAC).
o Rifapentine is a second-line drug that is given once weekly.
Mycolic acid synthesis inhibitors
Drug Spectrum of activity Side effect
Cycloserine 2nd line Anti-TB.
Isoniazid (PO, IM) Acid fast: M. tuberculosis and M. 1. Peripheral neuropathy as a
kansasii. consequence of drug-induced
deficiency in pyridoxine (vitamin B6):
▪ Dose-related paresthesia in
extremities.
▪ Administrated pyridoxine 20 mg/day
is recommended.
2. Hepatotoxicity.
3. Thrombocytopenia.
4. Hemolytic anemia (G6PD deficiency).
Others
Drug Spectrum of activity Side effect
Ethambutol Acid fast: M.tuberculosis, MAC, M. 1. Hepatotoxicity.
kansasii 2. Optic neuritis:
− Manifesting initially by red-green
color blindness.
− Loss of visual acuity (progression).
Pyrazinamide Acid fast: M. tuberculosis 1. Decreasing uric acid excretion.
2. Hepatotoxicity (dose related).
3. Joint pains.

PK/PD Characteristics
• Concentration dependent bactericidal antibiotics, with Post Antibiotic Effect (PAE):
⎯ Fluoroquinolone
⎯ AMG
⎯ Metronidazole
⎯ Daptomycin
• Time dependent bactericidal antibiotic:
⎯ Beta lactam
⎯ Carbapenem has PAE against Gm -ve.
• Time dependent slow onset bactericidal, with PAE:
⎯ Vancomycin
• Time dependent bacteriostatic, with PAE:
⎯ Macrolide
⎯ Tetracycline
⎯ linezolid

Yusuf Muhammad Garwan, PharmD intern – IAU (2019)

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Therapeutic Options
MSSA Anaerobes:
▪ Antistaph penicillins, Cefazolin (alternative if SE ▪ Penicillin G
is developed from antistaph PNC). ▪ Augmentin
▪ Piperacillin/tazobactam
MRSA: ▪ Cephamycin (cefoxitin, cefotetan)
❖ Community acquired MRSA: ▪ Carbapenems
▪ Doxycycline (IV, PO) ▪ Clindamycin
▪ Clindamycin (IV, PO) ▪ Tigecycline
▪ Bactrim (IV, PO) ▪ Metronidazole

❖ Hospital acquired MRSA: Enterococci:


o DOC: Vancomycin (IV) ▪ Ampicillin or amoxicillin.
o Alternatives:
▪ Ceftaroline (IV) VRE:
▪ Teicoplanin (IV) ▪ Ampicillin (if susceptible should be used,
▪ Telavancin, Dalbavancin, Oritavancin (IV) monotherapy or in combination with AMG or
▪ Daptomycin (IV) ceftriaxone)
▪ Linezolid, Tedizolid (IV, PO) ▪ Linezolid
▪ Tigecycline (IV) ▪ Daptomycin
▪ Omadacycline (IV, PO) ▪ Tigecycline
▪ Delafloxacin (IV, PO)
▪ Quinupristin/dalfopristin combination (IV) ESBL:
o DOC: Carbapenem (Ertapenem is preferred for
Pseudomonas aeruginosa: outpatient)
▪ Ciprofloxacin & levofloxacin (IV, PO) o Alternatives:
▪ Imipenem, meropenem, doripenem (IV) ▪ Ceftazidime/avibactam
▪ Piperacillin/tazobactam, Ticarcillin-clavulanate ▪ Ceftolozane/tazobactam
(IV) ▪ Tigecycline
▪ Ceftazidime, cefepime (IV) ▪ Eravacycline
▪ Ceftobiprole (IV) ▪ Piperacillin/tazobactam (UTI)
▪ Monobactam (IV) ▪ Nitrofurantoin (uncomplicated UTI)
▪ AMG (Amikacin, tobramycin, gentamicin, ▪ Fosfomycin (uncomplicated UTI)
Plazomicin) (IV)
Atypical bacteria:
MDR Pseudomonas aeruginosa: ▪ Fluoroquinolone
▪ Colistin (IV) ▪ Macrolide
▪ Ceftazidime-avibactam, ceftolozane-tazobactam, ▪ Tetracycline
Meropenem-vaborbactam (IV)
Acinetobacter: Listeria
▪ Imipenem, meropenem o DOC: Ampicillin
▪ Amikacin o Alternatives:
▪ Tigecycline ▪ Bactrim (SFX-TRM)
▪ Colistin ▪ Meropenem

Stenotrophomonas: Streptococci
o DOC: Bactrim (SFX-TRM) ▪ Penicillin (if susceptible), ceftriaxone.
o Alternatives:
▪ Levofloxacin Human, dog, or cat bite (contain anaerobic flora):
▪ Ceftazidime ▪ Augmentin
▪ Colistin ▪ Piperacillin/tazobactam.
▪ Minocycline
▪ Tigecycline
▪ Ticarcillin-clavulanate
Yusuf Muhammad Garwan, PharmD intern – IAU (2019)

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CRE:
▪ Serious infections:
o KPC:
▪ Ceftazidime-avibactam or Meropenem-vaborbactam
▪ Alternative: polymyxin-based regimen: colistin or polymyxin B + meropenem or tigecycline (GI, lung
infec.)
o Metallo-beta-lactamases:
▪ polymyxin-based regimen.
▪ Resistant to colistin: Ceftazidime-avibactam + aztreonam
▪ Potential alternative: combination regimen containing plazomicin (UTI)

▪ Acute simple cystitis:


⎯ Single active agent (eg, an AMG or fosfomycin).

▪ When B-lactam agents are used for CRE, prolonged infusion dosing can be considered.
▪ In case of lung infection with CRE, inhaled colistin can be used in conjunction with IV antibiotic.

Penicillin Allergies
Penicillin reactions can be classified as following:
1. Non-allergic reaction (nausea, diarrhea):
⎯ Beta-lactam antibiotics can be given normally (with attention to avoidance of similar SE).

2. Mild reactions WITHOUT features of IgE-mediated reactions:


⎯ Examples: Mild cutaneous reactions, such as mild drug eruptions.
⎯ Avoid penicillins, 1st & 2nd generation cephalosporins.
⎯ Treatment options:
▪ 3rd or higher-generation cephalosporins, carbapenems, or aztreonam.
▪ Penicillins, 1st & 2nd generation cephalosporins, GIVEN BY TEST DOSE PROCEDURE.

3. Reactions with features of IgE-mediated allergy:


⎯ Examples: flushing, pruritus, urticaria, angioedema, bronchospasm, laryngeal edema, and/or hypotension.
⎯ Treatment options:
▪ Aztreonam for Gm -ve, vancomycin or clindamycin for Gm +ve, or other non-beta lactam antibiotics.
▪ 3rd or higher-generation cephalosporins, carbapenems, GIVEN BY TEST DOSE PROCEDURE.

4. Serious type of delayed reaction:


⎯ Examples: Toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), Drug reaction with eosinophilia
and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DiHS), Serum sickness, Drug-induced
cytopenias, Drug-induced renal, hepatic other specific organ damage, hemolytic anemia.
⎯ Avoid penicillins, cephalosporins, and carbapenems.
⎯ Treatment options: aztreonam for Gm -ve, vancomycin or clindamycin for Gm +ve, or other non-beta lactam
antibiotics.

Yusuf Muhammad Garwan, PharmD intern – IAU (2019)

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Abbreviations: References:
▪ AMG: Aminoglycoside. ▪ Engelkirk, P. G. (2006). Burton’s microbiology for the
▪ AmpC: Class C B-lactamase. health sciences, ed. t. Edition.
▪ CAP: Community acquired pneumonia. ▪ DiPiro, J. T., Talbert, R. L., Yee, G. C., Matzke, G. R., Wells, B.
▪ CDAD: Clostridium difficle associated diarrhea. G., & Posey, L. M. (Eds.). (2014). Pharmacotherapy: a
▪ CRE: Carbapenem resistant Enterobacteriaceae. pathophysiologic approach (Vol. 6). New York: McGraw-
▪ C diffic: Clostridium difficle. ▪ Hill Education. Basic and Clinical Pharmacology - katzung -
▪ DDI: Drug-Drug Interaction. 12th Edition
▪ DOC: Drug of choice. ▪ Gallagher, J. C., & MacDougall, C. (2016). Antibiotics
▪ ESBL: Extended spectrum B-lactamase simplified. Jones & Bartlett Learning.
▪ Enteric GNR: Enteric gram-negative rods = ▪ David C Hooper. Fluoroquinolones. UpToDate online.
Enterobacteriaceae. ▪ Lowy, F. D., Sexton, D. J., & Baron, E. L. (2008). Treatment
▪ G6PD: Glucucose-6-phosphate dehydrogenase. of skin and soft tissue infections due to methicillin-
▪ GFR: Glomerular filtration rate. resistant Staphylococcus aureus in adults. Waltham, MA:
▪ Gm +ve: Gram positive bacteria UpToDate.
▪ Gm -ve: Gram negative bacteria. ▪ Kanj, S. S., & Sexton, D. J. (2015). Principles of antimicrobial
▪ KPC: Klebsiella pneumonia carbapenemase. therapy of Pseudomonas aeruginosa infections.
▪ IM: Intramuscular. UpToDate, Calderwood, SB (Ed), Bloom, A (Ed).
▪ IV: Intravenous. ▪ Munoz-Price, L. S., Jacoby, G. A., & Snydman, D. R. (2012).
▪ MDR: Multidrug-resistant. Extended-spectrum beta-lactamases. UpToDate online.
▪ MRSA: Methicillin-resistant staphylococcus aureus. ▪ Quale, J., Spelman, D., Hooper, D. C., & Bloom, A. (2016).
▪ MSSA: Methicillin-sensitive staphylococcus aureus. Overview of carbapenemase producing gram-negative
▪ N/V: Nausea & vomiting. bacilli. UpToDate: Waltham, MA, USA, Accessed on, 21.
▪ PAE: Post antibiotic effect. ▪ Blumenthal, K. G., & Solensky, R. (2018). Choice of
▪ PK/PD: Pharmacokinetic/Pharmacodynamic. Antibiotics in Penicillin-Allergic Hospitalized Patients.
▪ PO: Orally. Waltham, Mass: UpToDate.
▪ SE: Side effects. ▪ Micromedex. Internet database. Updated periodically.
▪ SFX-TRM: Sulfamethoxazole-Trimethoprim. ▪ Medscape [Database on the internet].
▪ UTI: Urinary tract infection. ▪ FDA drug labels.
▪ VRE: Vancomycin-resistant enterococcus.
▪ Tsuji, B. T., Pogue, J. M., Zavascki, A. P., Paul, M.,
▪ VRSE: Vancomycin-resistant staphylococcus aureus.
▪ XDR: Extensively drug-resistant. Daikos, G. L., Forrest, A., ... & Kaye, D. (2019).
International Consensus Guidelines for the Optimal
Use of the Polymyxins: Endorsed by the American
College of Clinical Pharmacy (ACCP), European Society
of Clinical Microbiology and Infectious Diseases
(ESCMID), Infectious Diseases Society of America
(IDSA), International Society for Anti‐infective
Pharmacology (ISAP), Society of Critical Care Medicine
(SCCM), and Society of Infectious Diseases
Pharmacists (SIDP). Pharmacotherapy: The Journal of
Human Pharmacology and Drug Therapy, 39(1), 10-
39.

Apologies for Any Mistake

Yusuf Muhammad Garwan, PharmD intern – IAU (2019)

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