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Spectrum of commonly used antibiotics
1. Spectrum of Commonly used
antibiotics
Dr. Mahen Kothalawala
MBBS, Diploma in Microbiology, MD, MPH(NZ)
Consultant Clinical Microbiologist
Teaching Hospital Kandy
SriLanka
2. Line up
• Antibiotics and Antibiosis
• Antibiotic General
• Classification of antibiotics
• Different types of antibiotic
– Penicillins
– Cephalosporins
– Other Cell-wall active drugs
– Amino glycosides
– Other Antibiotics – used in SL
• Some pharmacokinetic and Pharmacodynamic
Parameters
4. Antibiotics
• Are types of medications that destroy or slow
down the growth of bacteria.
• anti bios (GREEK)
– anti means "against",
– bios means "life“
• Any substance which used for this purpose is
called an antibiotic
5. Antibiosis
• Is a biological interaction between two or more organisms
that is
• detrimental to at least one of them
– or
• an antagonistic association between an organism and the
metabolic substances produced by another(antibiotic)
• Form of “Modified biological control” of organisms
• The relationship between an antibiotic and an infectious
organism is one form of antibiosis
6. An antibiotics are
• Different to other drugs
• Antibiotics-
– Act on targets in the bacterial cell/organisms
(Selectively toxic to bacteria/Organisms)
– While no effective action on Human cell(Selective
advantage)
• All other drugs-
– Act on targets in human cells/ Targets in human
cells. Antibiotics – no useful action on human cells
7. Antibiotics
• Are societal drugs –
– Resistance occur not only within the person taking the
antibiotic
– Harmful effect may transfer to others as well
– The resistance development is progressive and
independent
• “resistance gene passes very easily to other
individuals”
• Ingestion of one capsule of Amoxycillin – The
selected resistant organisms shed in stools nearly
three months- even after discontinuation of therapy
8. • No other category of drugs used in medicine
demonstrate this quality
9. Activity of an Antibiotics
• Desired Effect –Selective inhibition on bacterial
cell –Which provide selective advantage
• Undesired effects
• Adverse effects –
– Dose related (Predictable)
• Renal Failure with Aminoglycosides
• RF and oto-toxicity with Vancomycin
– Non dose related(Un predictable) –Idiosynchratic
reaction with chloramphenicol or Sulpha drugs
– Hyper sensitivity reaction of –penicillin
10. Why antibiotics need so much of
discussion?
1. We have discovered almost all naturally
occurring ones (No new ones)
2. Organisms readily become resistant to the
agents rendering them ineffective(Not
tachyphylaxis or not through enhanced
metabolism of drugs)
3. The resistance is transferable
The resistance mechanism/s readily become
transferable to intra species or inter species
14. Antibiotic Classification
On
1. Site of action (Most common and useful one)
2. Type of action (Bacteriostatic and
bacteriocidal)
3. Spectrum (narrow and broad)
17. C. Broad Spectrum vs Narrow Spectrum
•Carbepenams •Penicillin V and G
•Chloramphenicol •Lincosamides(Clindamycin)
•2nd 3rd 4th Gen Cephalosporiins •Glycopeptides(Vanco and Teicoplanin)
•3rd Gen Fluoroquinolones •Streptogramins
•Broad spectrum penicillins •Rifamycins
•Tetracyclines
•Daptomycin
Broad Spectrum Coverage Narrow Spectrum Coverage
25. Pen
G,V, Nafcillin, Oxacil
lin, FluClox and Clox
are bulky and less
soluble in water
Amph, Amoxy are
more polar
dissolves readily in
water due to amine
group attached
Tic and Pip are
made further polar
by adding COOH
and CO (NH)2 in to
R group
27. Spectrum of penicillins
• Narrow spectrum penicillin
– Pen G,Pen V
– Clox, Flu clox etc
– Mecillinam
• Broad Spectrum
– All others
• Extended Spectrum
28. Summary
• Penicillin G and V are useful only for
• Gram Positives and Anerobic Rods
– (Clostridium tetany and Clostridium perfringens)
• All gram negatives are resistant to penicillin G and V
• Cloxacillins (Inclusive of Flu clox, DiClox, Oxa and Naf cillin) are
exclusively for MSSA
– DOC of MSSA – Are Above
• Amphicillin and amoxycillin covers similar spectrum –only
difference is dosage frequency and interference to absorption by
food for amphicllin
• Becampicillin – are amphicllin esters which were formed to
overcome ↓of absorbtion due to food
– No advantage over each other
29. Broad spectrum penicillins
• Ticarcillin, Piperacillin, and Cabenicillin has
anti psudomonal activity
• Its spectrum is extended by adding Clav, Tazo
and Sulbactam to withstand enzymetic
degration
• Piperacillin is more potent than ticarcillin
against pseudomonas
• Mecillinam is exclusive for gram negatives
30. Borad spectrum penicillins are
• Need to be given high doses
– Piperacillin – 4.5g -3 to 4 times
– Ticarcillin as 3.2g- 3 to 4 times
• May causes electrolyte imbalance
31. • Piperacillin has greater intrinsic activity
against aerobic gram negative rods, than
Ticarcillin
• Adding Clavums will increase/expand the
spectru of penicillins.
32. G
Nafcillin
Oxacillin
Cloxacillin
Amphi-sul
Amphicillin
Amoxycillin
Flucloxacillin
Penicillin V &
Co-amoxyclav
Becamphicillin
X
X
X
X
O
Streptococcus Pyogenes
X
X
X
X
O
Streptococcus pneumoniae(DSSP)
Streptococcus pneumonia(DRSP)
O X
O X
O X
O X
O O
Enterococcus
X
Staphylococcus(MSSA)
O O
O O
O O
O
O O
Staphylococcus MRSA
X
X
X
Gram Positive Rods
X
X
X
O X
O O
Neisseria Menicngitidis
O
O
O
O
O
Neiseeria gonorhoea
X
X
X
O
O
Gram Negative rods(Sensitive)
X
X
O
O
O
Gram Neg Rods(βlactamase+)
O
O
O
O
O
Gram Negative –KPC Producers
O )
O
O
O
O
Gram Negative ESBL(
O
O
O
O
O
Pseudomonas
X
O
O
O
O
Acinetobacter sp
X
O
O
O
O
Atypical organisms
X
X
X
X
O
Spirochaetes(Lepto,, Treponema)
O
O
O
O
O
Spirochaete(Borrelia)
33. Ticarcillin
Mero/Ime
Amoxy-clv
Mezlocillin
Piperacillin
Aztreonam
Mecillinam
Piptaz-TacClav
Clavulinic Acid
X
X
X
X
O
O
O
Streptococcus Pyogenes
X
X
X
X
O
O
O
Streptococcus pneumoniae(DSSP)
X
X
X
X
O
Streptococcus pneumonia(DRSP)
X
X
X
X
O O
O O
Enterococcus
X
X
X Staphylococcus(MSSA)
O
O O
O O
O
O O
O
Staphylococcus MRSA
X
X
X
X
Gram Positive Rods
X
X
X
X
O O
O O
Neisseria Menicngitidis
X
X
X
X
O
O Neiseeria gonorhoea
X
X
X
X
X
X
O
Gram Negative rods(Sensitive)
X
X
X
X
O
O
Gram Neg Rods(βlactamase+)
O
O
O
O
O
O
Gram Negative –KPC Producers
)
#
X
O
O
O
O
O
Gram Negative ESBL(
X
X
X
X
O
O
Pseudomonas
O
O
O
O
O
O
Acinetobacter sp
O
O
O
O
O
O
Atypical organisms
-
X
X
O
O
O
Spirochaetes(Lepto,, Treponema)
-
O
O
O
O
O
Spirochaete(Borrelia)
34.
35.
36.
37. Hypersensitivty reaction to penicillin
• Major Ractions – Rare 1 in 10,000 doses
• Common reactions- MP rash with amphicillin,
sometimes subsequent exporsure may not
result rash
• 100% patients with IM, develop amphicillin
rash, if amp is given
• Should be very careful when labelling a
patient penicillin hypersensitive –Degree of
reaction should be noted down
38. Major hypesrsensitivity
• Anaphylaxis – 1/10000 patients
– Hives, angioedema, rhinitis, asthma, and anaphylaxis.
– 10% mortality rate.
– Anaphylaxis possible after negative skin testing.
– Avoid all other B-lactams.
– Mainly occur within first hour of exposure
Even with the first exposure to pen can get major HS reactions
Should be given in diagnosis card
For true HS patients –No beta lactam should be given
39.
40.
41. Cephalosporins
• Are semi-synthetic antibiotics derived from 7-
Amino cephalosporanic acid (7-ACA (cephem
nucleus).
• Similar to penicillins in
– mechanism of action,
– chemical structure, and
– toxicities
42. Traditionally divide into
• Generations
• On
• 1. Availabile form –IV or oral
• 2. Coverage
• 3. Ability withstand degradation by
ᵦ Lactamases
44. Gram Negative activity Improves
Gram Positive Activity Improves
First Second Third Forth
Generation Generation Generation Generation
Increasing activity against gram-negative bacterial and anaerobes
Increasing activity against Pneumococcus
Increasing ability to reach cerebrospinal fluid
45.
46. First generation cephalosporins
Clinical uses
• To treat gram-positives.
• Usually for non life threatening infections
• IV form is used to treat infections of mild mild
to moderate severe infection by sensitive
bacteria.
47. Agents
• Cephalexin
• Cephalothin
• Cephradine
• Cefazolin
• Cefadroxil
• Cefazolin- Main surgical prophylactic agent in
west (t ½ is 2 hrs)
48. Second generation cephalosporins
Pharmacological properties
They exhibit
• enhanced activity against gram-negatives
• First Gen< Second Gen < Third Gen
• but less than that of Third Gens
• More stability to bacterial β-lactamase
• Renal friendly than First Gen
49. Second generation cephalosporins
Clinical uses
• first choice drugs for gram-negative bacteria
• other indications are similar with First Gens
• In SL – Surgical prophylaxis (t1/2 is 80 min)
52. Third generation cephalosporins
Pharmocological properties
– least activity on gram-positive
• First Gen > Second Gen < Third Gen
– most active on Gram Negs
• First Gen < Second Gen < Third Gen
– high stability with β-lactamase; (Not to ESBL)
– Easily penetrate to different tissues (Including CSF)
– little kidney toxicity.
– Some third Gens are active against Pseudomonas (CAZ)
54. Third generation cephalosporins
Clinical uses
• Severe gram-negative resistant bacilli infection.
• Other complex infection
• Community acquired pneumonia and
meningitis
• SSTI
55. Fourth generation cephalosporins
– Cefepime
– Cefpirome
• have similar antibacterial activity with third
generation on most gram-negatives,
• more stable to β-lactamase.
57. Ceftobiprole
• Activity against
– MRSA,
– DRSP,
– Pseudomonas aeruginosa, and
– Enterococci
• Shown statistically non-inferiority to
Vancomycin and Ceftazidime combination
58. (PO
Cefoxitin
cEFIPIME
Ceftrixone
Cephalexin
Amoxycillin
Cefuroxime
Ceftibiprole
Ceftazidime
Cefazolin (IV);
X
X
X
X
X
X
X
O
Streptococcus Pyogenes
X
X
X
X
X
X
O
O
Streptococcus pneumoniae(DSSP)
X
X
X
X
Streptococcus pneumonia(DRSP)
X
O
O
O O
O
O O
O O
O O
Enterococcus
X
X
X
X
X
X
Staphylococcus(MSSA)
O X
X
O
O O
O
O
O
O
Staphylococcus MRSA
X
X
X
X
X
X
X
Gram Positive Rods
X
O X
X
X
O
O
O
O
Neisseria Menicngitidis
X
X
X
X
X
X
O
O
Neiseeria gonorhoea
X
X
X
X
X
X
O
Gram Negative rods(Sensitive)
X
X
X
O
O
X* O
Gram Neg Rods(βlactamase+)
?
O
O
O
O
X* O
O
X* O
Gram Negative –KPC Producers
? )
O
O
O
O
O
O
O
Gram Negative ESBL(
X
X
X
O
O
O
O
O
Pseudomonas
O
O
O
O
O
O
O
Acinetobacter sp
X
O
O
O
O
O
O
O
Atypical organisms
X
O
O
O
O
O
O
O
Spirochaetes(Lepto,, Treponema)
0
X
X
X
X
O
O
O
Anerobes
59. Other β-lactams
• Carbapenems
– Imipenem
– Meropenem
– Panipenem
– Ertepenam
• Has super broad antibacterial spectrum
• Resistant to activity of many bacterial enzymes
• Nearly all gram-negative and gram-positive bacteria
are treatable –EXCLUSION -Atypicals
• Carbapenems are one of the antibiotics of last resort
for many bacterial infections
60. Emerging issues
– Acinetobacter,
– Metalo betal lactamases producing organisms and
– Carbepenamases producing organisms
Are resistant to carbepenems
• Carbepenem resistance – An emerging grave
concern
• NDM-1 – Rapidly spreading resistant gene
61. • One case of KPC –Klebsiella pneumoniae
reported in THK recently
• Options for treatment?
62. • Rate of Carpepenem usage = Poor Infection
control activities
• Sorry state prevails in THK,( and in all around
SL)
• From here to where?
63. Other β-lactams
Monobactams
– Aztreonam
– Carumonam
• highly resistant to ß-lactamases.
• Effective in treating
– Gram-negative urinary tract infections,
– lower respiratory tract,
– skin, intra abdominal,
– gynecologic infections and septicemia.
64. Other β-lactams
β-lactamase inhibitors
• This kind of drug include
– clavulanic acid,
– sulbuctam and
– tazobactam.
• They are potent inhibitors of many kind of ß-
lactamases
• It increases the spectrum of penicillins
• Sulbactam has Acinetobactor coverage
65. Vancomycin
Only effective against gram-positive bacteria
Used to be the “Magic bullet” for methicillin-
resistant (MRSA)
Slowly bactericidal – agaist Staph
If, Staph are sensitive to Clox, DOC for that
become Clox (Not Vanc)
Poor oral absorption => Therefore available only
in IV form
For psudomembranous colitis (PMC) – oral form
available –NA in SL
66. Vanco
• Given for Penicillin allergic patients
• DOC for surgical prophylaxis in patients with a
history of severe penicillin allergy
• I have came across – 5 patients who developed
“allergic Reactions” to Vanc (Which is highly unlikely
• Could be “Rate related Anaphylactoid Reaction” –
For three patients treated well with Low rate
vacomycin (RMS)
67. Vanc
• Adverse effects.
– Fever, chills, phlebitis and red man syndrome.
• Slow injection and prophylactic antihistamines.
– Ototoxic – may potentiate known ototoxic agents.
• Renal excretion (90-100% glomerular filtration).
– Normal half-life 6-10 hours.
– Half life is over 200 hours in pts with ESRD
68. Teicoplanin
• Teicoplanin is similar to Vanc in action and
structure
• No RMS
• Can be given as a iv push
• Renal failure –Can give few doses safetly
69. Side effects
• Tinnitus and high tone deafness
• Dose related Renal toxicity
• Potentiating of activity of other renal toxic
drugs
• Red man Syndrome – Never to give as a
injection or as a bolus
70. Aminoglycosides
• Broad spectrum antibiotics (bactericidal)
• Penetration into cell requires an oxygen-dependent transport =>
anaerobes are resistant
• Poor oral absorption (very polar) => parenteral administration
• Narrow therapeutic range - severe side effects:
– Ototoxicity: destruction of outer hair cells in organ of Corti
– Nephrotoxicity: killing of proximal tubular cells
– Neuromuscular toxicity: blockage of presynaptic ACh release => respiratory
suppression
• Elimination almost completely by glomerular filtration
(impaired kidney function => concentration of AG increases => toxicity)
Drug Interaction with other antibiotics
• Chloramphenicol blocks this transport => inhibits AG uptake into bacteria;
• Penicillins weaken the cell wall => promote AG uptake)
71. • Adverse effects:
– Ototoxic – associated with high peak levels and prolonged
therapy. Pts on loop diuretics, vancomycin and cisplatin
are at higher risk.
• Cochlear and vestibular.
• Concentrates in endolymph and perilymph.
– Nephrotoxic.
• Proximal tubule damage.
72.
73. Amikacin
NetilmIicin
Gentamicin
0
0
0
Gram Positives
X
X
X
Staphylococcus(MSSA)
0
0
0
Staphylococcus MRSA
0
0
0
Gram Positive Rods
0
0
0
Neisseria Menicngitidis
0
0
0
Neiseeria gonorhoea
X
X
X
Gram Negative rods(Sensitive)
X
X
X
Gram Neg Rods(βlactamase+)
x
X
X
Gram Negative –KPC Producers
X
X
X
)
Gram Negative ESBL(
X
X
X
X Pseudomonas
X
X
Acinetobacter sp
Aminoglycosides
0
0
0
Atypical organisms
0
0
0
Spirochaetes(Lepto,, Treponema)
0
0
0
anerobes
0
0
X
Tuberculosis(MDR)
74. Macrolides
• Antibacterial spectrum:
– Erythromycin:
• Gram positives: Staph.(Not MRSA), Strep., Bordetella, Treponema,
Corynebacteria.
• DOC to Atypicals: Mycoplasma, Ureaplasma, Chlamydia
– Clarithromycin:
• Similar to erythromycin.
• Increased activity against gram negatives (H. flu, Moraxella) and
atypicals
– Azithromycin:
• Decreased activity against gram positive cocci.
• Increased activity against H. flu and M. cat
• Salmonella typhi.
75. • Adverse effects.
– 10-15% of pts do not finish the prescribed course of
erythromycin because of GI distress.
– Jaundice
– Ototoxic (high doses)
• Drug interactions
– Oxidized by cytochrome p-450.
– Inhibits other substrates and increases their serum
concentrations.
• Theophylline, warfarin, astemizole, carbemazepine, cyclosporine,
digoxin, terfenadine
76. Clindamycin
• Used for deep neck space infections, chronic
tonsillo-pharyngitis, odontogenic
abscesses, and surgical prophylaxis in
contaminated wounds.
• Concomitant use of macrolides or
Chloramphenicol adds no benefit.
• Resistance: MLSB – ribosomal alteration.
77. Clinda
• Pseudomembranous colitis – clindamycin > cephalosporins
(Ceftin) > aminopenicillins.
– Abdominal pain, fever, leukocytosis, bloody stool…
– Diarrhea commonly develops on days 4-9 of treatment.
– Typically resolves14 days after stopping the antibiotic.
– Treat with Flagyl (PO or IV).
– Life threatening cases can be treated with oral Vancomycin.
78. FQ
• Ciprofloxacin (Cipro; IV $103.75/day; PO/Topical; Restricted use @
UTMB), Ofloxacin (Floxin; Topical $60.90), Levofloxacin
(Levaquin; IV 15.62/day; Oral $6.72/day).
• Synthetic derivatives of nalidixic acid.
• Inhibits DNA gyrase, causing permanent DNA cleavage.
• Resistance:
– DNA Gyrase mutations
– Cellular membrane efflux mechanisms.
– Decreased number of porins in target cells.
• Wide distribution - CSF, saliva, bone, cartilage
79. Coverage FQ
• Effective vs. gram +, gram -, atypicals, and Pseudomonas.
• Decreased activity against anaerobes.
• Respiratory quinolones (levofloxacin).
– Active against Strep (including penicillin-resistant forms), S. aureus (including
MRSA), H. flu, M. cat (including penicillin-resistant strains), and atypicals.
– Used in AOM, sinustiis, pharyngitis…
• Antipseudomonas quinolones (ciprofloxacin/ofloxacin)
– Active against Pseudomonas, H. flu, M. cat.
– Strep pyogenes, Strep pneumoniae, and MRSA are resistant.
– Used in children with Cystic Fibrosis.
– Topicals used for otitis media.
• Levofloxacin and Moxifloxacin have increased Staph activity even against
cipro-resistant strains.
80. How shall one select an antibiotic for
treatment
• Ten rules in antibiotic prescription
81. Ten Rules in antibiotic prescriptions
1. Antibiotics indicated on Clinical Grounds?
2.Have appropriate investigations performed?
3.What organisms are likely cause?
4.Which Agent is best?
5.Is an appropriate combinations best?
6.Is any host factors relevant?
7.What is the best route of Administration?
8.What is the appropriate dose?
9.Can therapy be modified when lab results are available?
10.What is the optimal duration of therapy?
81
