11. Linezolid
• Against all major Gram-positive pathogens of humans
(including staphylococci, enterococci, streptococci, Bacillus
species, Corynebacterium, and Listeria monocytogenes),
good activity against many Gram-positive anaerobes, and
activity against a number of mycobacteria and Nocardia
species, also MRSA
• infections of the skin and pneumonia.
• As a protein synthesis inhibitor. Linezolid is an
oxazolidinone antibiotic
• complicated skin and skin structure infections (cSSSI)
• an alternative to vancomycin in the treatment of febrile
neutropenia in cancer patients when Gram-positive
infection is suspected
12. • Linezolid is considered bacteriostatic against most organisms.
• Linezolid has no clinically significant effect on most Gram-negative
bacteria.
• Adverse effects:
1. pancreatitis, and elevated transaminases, which may be a sign of
liver damage.
2. Bone marrow suppression, characterized particularly
by thrombocytopenia , NEUTROPENIA
3. Linezolid is a weak monoamine oxidase inhibitor (MAOI),
4. Linezolid therapy has been associated with hyperlactatemia,
usually after prolonged treatment
5. long-term use of linezolid (usually many months of treatment)
may be associated with the development of severe peripheral and
optic neuropathy,
13. Linezolid is a weak monoamine oxidase
inhibitor (MAOI),
the potential for interaction with adrenergic
and serotonergic agents exists. Several case
reports of serotonin syndrome (fever,
agitation, tremors, and mental status changes)
secondary to an interaction between linezolid
and selective serotonin reuptake inhibitors
(SSRIs) have been identified.
14. • Linezolid is approximately 30% protein bound
and penetrates quickly into bone, fat, and
muscle, achieving 50% to 60% of serum
concentrations in bone and 90% to 95% in
muscle.Cerebrospinal penetration has been
documented in patients with meningitis at a
fluid/plasma ratio around 1
15. DOSES:
• available as an IV injection for infusion (in singleuse
infusion bags, at a concentration of 2 mg/ml), in tablets
(400 or 600 mg), and in an oral suspension (granules
resuspended in 123 ml of water to give a concentration of
20 mg/ml).
Dose: 600mg iv bd for 10 to 14 days
• no dose reduction required in renal and hepatic failure.
• The IV injection is given over 30–120 minutes, whereas the
oral formulations can be taken with or without food.
• linezolid should be avoided in pregnancy. Linezolid passes
into breast milk, and breastfeeding should be stopped
while lactating females are receiving linezolid.
16. VANCOMYCIN
• Vancomycin is a glycopeptide.
• bactericidal against most gram-positive organisms.
• Penetration is greater than 75% serum concentrations
into ascitic, pericardial, and synovial fluids,
approximately 50% into pleural fluid, and 30% to 50%
into bile.
• Vancomycin does not penetrate well into aqueous
humor or noninflamed meninges; however,
penetration ranges from 1% to 37% of serum
concentrations in the setting of meningeal
inflammation.
17. vancomycin
• the treatment of septicemia and lower
respiratory tract, skin, and bone infections caused
by Gram-positive bacteria.
• methicillin-resistant S. aureus (MRSA)
• Treatment of pseudomembranous colitis caused
by C. difficile; oral treatment
• Vancomycin is active against anaerobic gram-
positive organisms such as Peptostreptococcus
spp., Propionibacterium spp., Eubacterium spp.,
Bifidobacterium spp., and most Clostridium spp.,
including C. difficile.
18. • acts by inhibiting proper cell wall synthesis in
Gram-positive bacteria.
• Side effects
1. erythema multiforme,
2. red man syndrome,
3. thrombocytopenia, neutropenia, leukopenia
4. tinnitus,dizziness and/or ototoxicity,
and DRESS syndrome
19. • Dosing considerations
1. 1gm iv bd infuse over 2 hr
2. The only approved indication for oral
vancomycin therapy is in the treatment of
pseudomembranous colitis
3. via nebulizer, for treatment of various infections
of the upper and lower respiratory tract
4. central lines or infusion ports should be used.
5. Dose adjustment required in renal failure
20. Teicoplanin
• semisynthetic glycopeptide antibiotic with a
spectrum of activity similar to vancomycin
• inhibit bacterial cell wall synthesis
• trade name Targocid.
• Oral teicoplanin has been demonstrated to be
effective in the treatment
of pseudomembranous colitis and Clostridium
difficile-associated diarrhoea, with
comparable efficacy with vancomycin.
21. • effective antimicrobial against Gram-positive
bacteria including MRSA
• DOSE: 400 MG IV BD F/B 400MG OD infuse
over 30 min.
• dose reduction required in renal faiure.
• A/E disturbance in liver enzyme, renal
impairment, toxic epidermal necrolysis.
22. CLINDAMYCIN
• Clindamycin is active against most Grampositive
aerobic bacteria, many anaerobes, and protozoa.
• Aerobic Gram negative bacteria are usually not
susceptible.
• The lincosamides inhibit protein synthesis.
• Clindamycin can be given intramuscularly,
intravenously, orally, and is also available as a
vaginal ovule or for topical administration as a
wipe, solution, gel, lotion, foam, or cream.
23. DOSE
• ORAL ADMINISTRATION: of 150 mg every 6 hours is
recommended for adults, but this may be increased to 300
or 450 mg every 6 hours
• PARENTERAL ADMINISTRATION: 600–1200 mg/ day given in
two to four divided doses. For intravenous administration of clindamycin
phosphate, the concentration of clindamycin in the fluid for infusion should not exceed 18
mg/ml and infusion rates should not exceed 30 mg/min
• 600 MG TDS IV INFUSE OVER 30 MIN
• Clindamycin undergoes minimal urinary excretion, mild to
moderate renal failure, dosage adjustments for clindamycin
are not necessary.
• Clindamycin is metabolized and excreted by the liver;
therefore dosage adjustments are recommended for
hepatic dysfunction
24. • ADVERSE REACTIONS:
1. use of clindamycin (as with any antibiotic)
may give rise to overgrowth of
nonsusceptible organisms, particularly fungi.
2. Hepatotoxicity
25. • CLINDAMYCIN GOOD FOR:
1. Skin and connective tissue infections
2. necrotizing fasciitis and toxic shock syndrome
3. Bone and joint infections
4. Toxoplasmosis
5. Malaria
6. Gas gangrene (clostridial myonecrosis
7. SINUSITIS
26. Azithromycin
• Belong to macrolide group.
• It accumulates significantly intracellularly.
• Macrolides are bacteriostatic antibiotics.
• ANTIMICROBIAL ACTIVITY:
1. moderately broad spectrum of activity.
2. most Gram-positive.
3. only selected Gram-negative organisms, as well
as several bacteria responsible for intracellular
infection, such as Mycobacteria spp., Chlamydia
spp., or Legionella spp.
27. • Gram positive anaerobe coverage present.
• Azithromycin is more active than erythromycin toward
Gram-negative bacteria.
more active against
Neisseria meningitidis and N. gonorrhoeae.
• also shows activity against nontuberculous
mycobacteria, including Mycobacterium avium
complex (MAC), other nontuberculous mycobacteria,
such as M. kansasii,
• Active against Mycoplasma pneumoniae, M.
genitalium, Chlamydia.
29. DOSAGE
• ORAL AND INTRAVASCULAR
• FOR i.v, diluted to 1 mg/ml for administration
over 3 hours.
• 500 mg od.
• No dosage adjustment is required in patients with
renal insufficiency.
• well tolerated with few side effects: mainly GI
• Transaminase elevation occurs during
azithromycin treatment in 7% of patients.
• prolongation of the QT interval.
30. • CLINICAL USES OF THE DRUG
1. Upper respiratory tract infections
2. ACUTE BACTERIAL SINUSITIS
3. Lower respiratory tract infections
4. PULMONARY MYCOBACTERIUM AVIUM
COMPLEX (MAC) DISEASE
5. SALMONELLA TYPHI AND SALMONELLA
PARATYPHI
6. CHOLERA
33. AZTREONAM
• Aztreonam is the only monobactam currently available.
• safe to administer to patients with allergies to other
beta-lactams
• Monobactams inhibit cross-linking of peptidoglycan in
the cell wall, leading to autolysis and cell death.
• Spectrum
1. Good: Pseudomonas, most GNRs
2. Moderate: Acinetobacter
3. Poor: Gram-positive organisms, anaerobes
34. • Dose: 1 to 2gm iv tds
• max 8 gm/day
• Renal impairment dose reduction required
• given by injection into a
vein or muscle or breathed in as a mist.
• Nebulized forms: bronchiectasis, ventilator-associated pneumonia,
chronic obstructive pulmonary disease, mycobacterial disease. inhaled(trade
name Cayston) using an ultrasonic nebulizer.
• Synergism between aztreonam
and arbekacin or tobramycin against P.
aeruginosa has been suggested
35. cephalosporins
• 1st gene GP GN
• ++++ +
• 2nd gen
• +++ ++
• 3rd gen
• ++ +++
• 4th gen
• ++ ++++
• anti-MRSA
36. FIRST GENERATION
• cefazolin, cephalexin, cefadroxil, cephalothin
• most commonly used class of antibiotics in the
hospital.
• used immediately prior to surgery to prevent
surgical site infections
• Spectrum
1. Good: MSSA, streptococci
2. Moderate: some enteric GNRs
3. Poor: enterococci, anaerobes, MRSA,
Pseudomonas
37. • Cephalexin and cefadroxil are available orally;
the others are parenteral.
• GOOD FOR:Skin and skin structure infections, surgical
prophylaxis, staphylococcal bloodstream infections,
osteomyelitis, and endocarditis
38. 2ND GENERATION
• cefuroxime, cefoxitin, cefotetan, cefprozil,
loracarbef, cefmetazole, cefonicid,
cefamandole, cefaclor.
• Compared with first-generation
cephalosporins, second-generation agents
have better Gram-negative activity and
somewhat weaker Gram-positive activity.
• particularly active against Haemophilus
influenzae and Neisseria gonorrhoeae.
39.
40. 3RD GENERATION
• parentral: ceftriaxone, cefotaxime,
ceftazidime, cefoperazone.
• Oral: cefdinir, cefpodoxime, cefixime,
ceftibuten,
• Third-generation cephalosporins have greater
Gram-negative activity than the first- and
second-generation drugs.
• broad-spectrum agents.
41. • Spectrum
• Good: streptococci (except ceftazidime, which
is poor), enteric GNRs, Pseudomonas
(ceftazidime only)
• Moderate: MSSA (except ceftazidime, which is
poor)
• Poor: enterococci, Pseudomonas (except
ceftazidime), anaerobes, MRSA
42. • What They’re Good For
1. Lower respiratory tract infections,
2. pyelonephritis,
3. nosocomial infections (ceftazidime)
4. , Lyme disease (ceftriaxone),
5. meningitis,
6. gonorrhea,
7. skin and skin structure infections,
8. febrile neutropenia (ceftazidime).
43. 4th generation
• Agent: cefipime, cefpirome
• broadest-spectrum cephalosporin, with activity
against both Gram-negative organisms, including
Pseudomonas, and Gram-positive organisms.
• Spectrum
1. Good: MSSA, streptococci, Pseudomonas,
enteric GNRs
2. Moderate: Acinetobacter
3. Poor: enterococci, anaerobes, MRSA
46. CEFTRIAXONE
• a third-generation or extended-spectrum
cephalosporin.
• inhibition of bacterial cell wall synthesis.
• good activity against many wildtype Gram-
negative organisms with reasonable activity
against Gram-positive organisms.
• Notable exceptions include a lack of consistent
activity against Pseudomonas aeruginosa and
enterococci
• No ANAEROBIC activity.
47. DOSAGE
• not absorbed after oral administration, and so
it must be administered by either the
intramuscular (i.m.) or intravenous (i.v.) route.
• be administered i.v. by infusion over a period
of 30 minutes.
• adult dose is 1–2 g/day given once daily (or
inequally divided doses twice daily).
• pediatric dosage is 50–100 mg/kg body weight
daily, given in one or two divided doses
48. • Dose adjustment for ceftriaxone in patients
with renal impairment is unnecessary.
• dosing adjustments (with a ceftriaxone dosage
up to 2 g/day) are not required in patients
with impaired hepatic function.
49. Cefoperazone and Cefoperazone–
Sulbactam
• third-generation cephalosporin
• ANTIMICROBIAL ACTIVITY:
1. good gram negative coverage with moderate
gram positive coverage.
2. some Gram-positive anaerobes, such as
Peptococcus, Propioni bacterium spp., and
Clostridium perfringens, are cefoperazone
susceptible;
50. DOSAGE
• The usual adult dosage of cefoperazone is 1–2
g, given i.m. or i.v. every 12 hours.
• For serious infections, the total daily adult
dose can be increased to 6–12 g, given in two,
three, or four divided doses.
• infused more slowly over intervals of 30–60
minutes.
51. • As biliary excretion is the primary route of cefoperazone
elimination, dosage modification is unnecessary in patients
with any degree of renal failure.
• However, the clearance of sulbactam is significantly
decreased in patients with renal failure. Adjustment of the
dosing regimen of cefoperazone–sulbactam for patients
with estimated creatinine clearance of < 30 ml/minute can
be made to compensate for reduced sulbactam total body
clearance.
• Under these conditions, the combination may be given
• once daily, with an additional dose of cefoperazone (given
alone) 12 hours later.
52. • CLINICAL USES OF THE DRUG
1. Intraabdominal infection.
2. Febrile neutropenia.
3. Acinetobacter infections.
4. Hospital-acquired pneumonia.
53. POLYMYXIN
• a group of antibiotics, named A, B, C, D, E, and
so on.
• only polymyxin B and E (the latter also known
as colistin) are used clinically.
• The polymyxins have antibacterial activity
against Gram negative organisms and are not
active against Gram-positive bacteria.
• There is cross-resistance between polymyxin B
and colistin
54. antimicrobial activity
• Gram-positive bacteria are resistant to the polymyxins.
• Activity against Gram negative organisms
P. aeruginosa and Acinetobacter, Escherichia coli,
Enterobacter species, and Klebsiella species, active
against Haemophilus influenzae and Bordetella
pertussis.
The pathogenic Neisseria spp. (mening o cocci and
gonococci) and the Brucella spp. are resistant .
Salmonellae and shigellae are susceptible, but Proteus
species are usually resistant .
• The polymyxins are rapidly bactericidal against
susceptible organisms,
55. DOSES
• parenteral products of polymyxins available for use.
• POLYMYXIN B SULFATE:each vial contains 500,000 units,
which is equivalent to ~ 50 mg.
• COLISTIN METHANESULFONATE:One million IU corresponds
to approximately 33 mg CBA(colistin base activity) and
approximately 80 mg of the chemical CMS.
• the polymyxins are administered parenterally, most
typically by the intravenous route,AND INTRAMUSCULAR
They are also administered by the intrathecal or
intraventricular route for the treatment of central nervous
system infections and in aerosolized form into the lungs for
the treatment of respiratory infections;
56. POLYMYXIN B SULFATE
• The usual approved intravenous dosage in product
information for adults is 15,000–25,000 units per kg
body weight per day MAX UPTO 30,000 UNITS PER
KG.i.e. 5 lakh unit tds.
• The clearance of polymyxin B is not affected by kidney
function, and therefore a reduction in daily dose will
result in a decrease in plasma concentration exposure,
which may compromise the antibacterial effect.
• infused over a period of ~ 60 minutes
• Polymyxin B has been used off-label as inhalation
therapy, 5LAKH units bd, beta2 agaoinst s/b nebulised
before to prevent the bronchospasm.
57. COLISTIN METHANESULFONATE
• Conversion of CMS to colistin commonly occurs quite slowly, it may take many
hours to achieve plasma colistin concentrations that are efficacious. Therefore
it is advisable to initiate therapy with a loading dose of CMS a loading dose of
9 million.
• creatinin clearnace dose/DAY in 3 doses
>50 9 MIU
30 TO 50 5.5 TO 7.5
10 TO 30 4.5 TO 5.5
< 10 3.5
• loading and daily maintenance doses are administered as a short-term
infusion (e.g. over 30–60 min).
• CMS by intramuscular injection is not recommended.
• intraventricular or intrathecal administration of CMS in a dose of 125,000 IU
per day FOR MENINGITIS.
• Aerosolized CMS has been used for many years, 1–2 million IU two to three
times per day.
58. ADVERSE REACTIONS AND TOXICITY
• NEPHROTOXICITY
• higher risk of nephrotoxicity with CMS
compared with polymyxin B
59. PIPRACILLIN TAZOBACTAM
• is a beta-lactam/ beta-lactamase inhibitor
combination.
• Piperacillin is an aminobenzyl-penicillin derivative.
• Piperacillin is bactericidal due the irreversible inhibition
of penicillin-binding protein enzymes (PBPs), which
results in the loss of cell wall integrity through a
complex mechanism involving autolysins.
• While tazobactam alone lacks any intrinsic activity, its
addition to piperacillin leads to increased stability of
piperacillin against beta-lactamases.
60. • of activity against the majority of Gram-
positive bacteria, Gram-negative bacteria, and
anaerobes, pseudomonas.
• Resistant strains include methicillin resistant
Staphylococcus aureus, Enterococcus faecium,
Stenotrophomonas maltophilia as well as
some Pseudomonas, Citrobacter, and
Enterobacter species.
61. DOSAGE
• The usual dose is 13.5 g divided into three or
four doses daily (most commonly 4.5 g 8/24 or
3.375 g 6/24).
• more commonly over 30 minutes.
• Dose reduction required in renal failure.
62. MEROPENAM
• It is rapidly bactericidal.
• broad-spectrum parenteral carbapenem with
antimicrobial activity against a wide range of
Gram negative and Gram-positive bacteria,
including anaerobes.
• class have excellent in vitro activity against
anaerobic organisms, exceptions for Gram-
positive anaerobes include Clostridium difficile
and Lactobacillus.
• impaired cell wall synthesis ensues, leading to
inhibited growth and cell lysis.
63. DOSAGE
• only in parenteral form.
• dosed at 500–2000 mg, depending on the
infection type ; every 8 hours as an intravenous
infusion over 15–30 minutes.
• 1 to 2 gm iv tds over 30 min
• meropenem is primarily eliminated unchanged in
the urine, accumulation is seen in patients with
renal impairment, dose modification required.
• No dosage adjustment is needed in patients with
liver impairment.
64. • Lower the threshold for seizure imipenem>
mero.
• MEROPENEM–VABORBACTAM
• beta-lactamase inhibitor compounds with
activity against carbapenemases, agent
vaborbactam, a cyclic alpha-acylamino
boronic acid, is a potent inhibitor of serine
carbapenemases.
65. IMIPENEM–CILASTATIN
• ANTIMICROBIAL ACTIVITY: active against a broad
range of Gram-positive and Gram-negative
bacteria, including both aerobes and anaerobes.
• Spectrum
1. Good: MSSA, streptococci, anaerobes, enteric
GNRs, Pseudomonas (not ertapenem),
Acinetobacter (not ertapenem), ESBL-producing
GNRs
2. Moderate: enterococci (not ertapenem)
3. Poor: MRSA, penicillin-resistant streptococci
66. • Klebsiella pneumoniae is the most frequently
reported imipenem resistant
Enterobacteriaceae.
• Imipenem, like all other beta-lactam agents,
inhibits bacterial cell wall synthesis.
• rapid bactericidal effect to both rapidly and
slowly growing bacteria.
67. • Imipenem is most commonly administered in
a dosage of 500 mg every 6 hour or less often
1 g every 8 hour, intravenously.
• Dose modification required in renal failure.
68.
69. Aminoglycoside
GENTAMICIN
• Mixture of relatively equal amounts of three
natural aminoglycosides, gentamicin c1
, gentamicin c2, and gentamicin c1a.
• used clinically as the sulfate salt.
• the antibiotic spectrum of gentamicin comprises
mainly gram- negative aerobic bacilli.
• anaerobic bacteria are not susceptible to
gentamicin
70. DOSAGE
• recommended is 4.0–7.0 mg/ kg i.m. or i.v. per
day administered as a single dose or divided
into two or three equal doses.
• Intravenously, the drug has usually been given
as a 30-minute infusion.
• Patients with impaired renal function require
a modified dosage schedule.
71. ADVERSE REACTIONS AND TOXICITY
• Ototoxicity:The drug can cause both vestibular and
cochlear toxicity.
• Nephrotoxicity:Gentamicin is selectively concentrated
in renal cortical cells, and it can cause functional and
structural damage to the proximal tubules, higher
doses acute tubular necrosis.
• The most common clinical manifestation of gentamicin
nephrotoxicity is a gradual onset over several days of
nonoliguric renal failure with proteinuria and
increasing blood urea and serum creatinine values. This
appears to be dose related and is usually reversible.
72. • Neurotoxicity and neuromuscular
blockade:Gentamicin, in common with other
aminoglycosides, can cause neuromuscular
blockade
73. Tobramycin
• Tobramycin is used clinically both as a sulfate salt
and in a nebulizer solution in sodium chloride and
without preservatives for inhalation.
• It is a drug similar to gentamicin but its
advantages include greater intrinsic activity
against Pseudomonas aeruginosa, activity against
some gentamicin resistant P. aeruginosa and
Acinetobacter baumannii strains, and lesser
nephrotoxicity.
74. • Similar to gentamicin, tobramycin has only a
low degree of activity against Grampositive
bacilli and is inactive against anaerobic Gram-
positive organisms
75. DOSAGE
• The usually recommended dosage of
tobramycin is 4.0–7.0 mg/kg i.m. or i.v. per
day administered as a single dose or divided
into two or three equal doses.
76. AMIKACIN
• Bactericidal antibiotic
• bound to specific 30S-subunit ribosomal proteins, leads to
protein synthesis inhibition.
• Overall effect is irreversible and leads to cell death.
• Penetration into bacterial cell is dependent upon
maintenance of a polarized membrane and an oxygen
dependent active processes.
• Inhibitors of bacterial cell wall (beta lactams, vancomycin)
enhance it’s entry exhibit synergism.
• The cidal action is concentration dependent.
• It also exert long and concentration dependent post antibiotic
effect.
77. • Spectram: mainly gram- negative aerobic bacilli.
• active against all the Enterobacteriaceae such as
Escherichia coli, Enterobacter, Klebsiella, Proteus,
Salmonella, Shigella, Providencia, Serratia, Citrobacter,
and Yersinia spp.
• Pseudomonas aeruginosa is susceptible to amikacin.
• Acinetobacter baumanii is usually amikacin susceptible,
but resistant strains have increased in prevalence.
• Amikacin, like kanamycin, is active against the Neisseria
spp. (meningococci and gonococci) and Haemophilus
influenzae.
78. amikacin
• Burkholderia cepacia and Stenotrophomonas
maltophilia are usually resistant to amikacin.
• anaerobic bacteria are not susceptible to
amikacin.
• GRAM-POSITIVE BACTERIA: Staphylococcus
aureus and S. epidermidis, including penicillin G–
resistant strains of both, are usually susceptible
to amikacin.
• Other Gram-positive cocci, such as Streptococcus
pyogenes, S. pneumoniae, and Enterococcus
faecalis, are resistant to amikacin
79. • Mycobacterium tuberculosis is amikacin
susceptible.
• Mycobacterium avium complex (MAC) is
usually susceptible.
80. DOSAGE
• The dosage of amikacin usually recommended
is 15–20 mg/ kg i.m. or i.v. per day
administered as a single dose or in two
divided doses. 1gm od OR 500mg bd
• Intravenously, the dose is dissolved in 30–50
ml of i.v. fluid and then infused over 30 min.
• Dose modification required in renal failure.
81. • Once-daily amikacin administration may be
slightly less nephrotoxic than classic 12-hour
dosing (Rougier et al., 2003), and some
investigators have also found it clinically
slightly more efficaceous (Maller et al., 1988;
Maller et al., 1993; Garraffo et al., 1990;
Beaucaire et al., 1991; Marik et al., 1991a;
Marik et al., 1991b).
82. FLUROQUINOLONES
• Bactericidal agent.
• Blocks bacterial dna synthesis.
• They can enter cells easily via porins and are
used to treat intracellular pathogens
(Legionella, pneumophila and Mycoplasma
• Resistance to one FQL confers cross
resistance to all members of the class.
83. classification
Class/generation name spectrum
1[Quinolone] Nalidixic acid Cinoxacin Gram-ve but not
Pseudomonas species
2 Norfloxacin
Ciprofloxacin
Ofloxacin
Gram- ve(including
Pseudomonas species),
some Gram+ (S. aureus)
and some atypicals
3 Levofloxacin
Sparfloxacin
Moxifloxacin
Gemifloxacin
Same as 2nd generation
with extended Gram+ve
and atypical coverage
4 Trovafloxacin Same as 3rd generation
with broad anaerobic
coverage
84. • Most of fluoroquinolones eleminated by renal
mechanism so adjustment required in patients
with creatinine clearance <50 ml/min.
• Limited CSF penetration.
• Contraindication
• Childrens
• Pregnancy Lactation
• Epilepsy
• QTc prolongation
85. Ciprofloxacin
• 2nd generation fluoroquinolone
• Mainly effective against G –ve bacteria :
Enterobacteriacae H. influenzae M.
catarrhalis Campylobacter Pseudomonas
N. gonorrheae
Intracellular pathogens
M. Tuberculosis Mycoplasma Chlamydia
Legionella Brucella
• Not effective against G+ and anaerobes
86. DOSAGE
• Usual duration is 7-14 days.
• ORAL ADMINISTRATION: The usual adult oral
dose of ciprofloxacin ranges from 250 to 750
mg twice daily, depending on the type and
severity of infection.
• INTRAVENOUS ADMINISTRATION: 400 mg iv
bd
87. Levofloxacin
• 3rd generation fluoroquinolone
• Spectrum: Gram-ve, Gram+ve (S. aureus including
MRSA & S. pneumoniae) and Legionella pneumophila,
atypical resp. pathogens, Mycobacterium tuberculosis.
• Levofloxacin is most potent against enteric Gram-
negative bacteria with lower potency against P.
aeruginosa.
• Levofloxacin has improved activity over ciprofloxacin
against many Gram-positive bacteria, but two- to
fourfold less active than gatifloxacin and moxifloxacin.
88. • Activity is also excellent against “atypical”
respiratory pathogens such as Mycoplasma
pneumoniae, Chlamydia pneumoniae, and
Legionella spp.
89. DOSAGE
• 500 or 750 mg once daily.
• levofloxacin is largely renally excreted, and
dosage reductions should be made in patients
with creatinine clearances below 50 ml/min.
• No dosage adjustment is needed with hepatic
dysfunction unless renal function is also
altered.
90. TIGECYCLINE
• Tigecycline is the first glycylcycline that became
available for clinical use and is a member of the
tetracycline family.
• Tigecycline is a semisynthetic derivative of
minocycline.
• tigecycline inhibits bacterial protein synthesis
through its binding action on the bacterial 30S
ribosomal subunits.
• Tigecycline is only available for parenteral
administration.
91. • Spectrum: tigecycline
• Good: atypicals, enterococci (including VRE),
staphylococci (including MRSA), S.
pneumoniae
• Acceptable: most GNRs, anaerobes
• Poor: NOT ACTIVE AGAINST Pseudomonas,
Proteus, Providencia
92. • Tigecycline is active against most Gram-positive
and Gram-negative anaerobes, showing in vitro
activity against Clostridium difficile,
Fusobacterium spp., Prevotella spp.,
Porphymymonas spp., Lactobacillus spp.,
Actinomyces spp., Veil lo nella spp., and the
Peptostreptococcus spp.
• ATYPICAL BACTERIA-Mycoplasma hominis;
Mycoplasma pneumoniae; Chlamydophyla
pneumoniae; Chlamydia trachomatis
93. • tigecycline has activity against the rapidly
growing mycobacteria—M. fortuitum group,
M. abscessus, M. chelonae, M.
immunogenum, and M. smegmatis.
• Unfortunately, no data are available for M.
tuberculosis.
94. • DOSAGE;
• Tigecycline is available for i.v. use only.
• The recommended dosage for the treatment of
complicated intra-abdominal, skin/skin structure infections,
and community-acquired pneumonia is 100 mg as a
starting dose, followed by 50 mg every 12 hours for 5–14
days. The infusion time is 30–60 minutes.
• dosing regimes of 200 mg followed by 100 mg have been
used succesfully for critically ill patients ,patients with
hospital-acquired pneumonia (HAP) and ventilator-
associated pneumonia (VAP) and urinary tract infections
with MDR pathogens
95. • Tigecycline should not be given to children, because there
are no data on safety and efficacy in relation to children <
18 years of age.
• Tigecycline has been shown to be safe in patients with
renal impairment and in patients undergoing hemodialysis.
no dose adjustment is necessary in patients with renal
failure.
• Therefore, no dose adjustments for tigecycline are
necessary in patients with mild to moderate liver
dysfunction. In patients with severe hepatic dysfunction
(Child Pugh class C), the maintenance dose of tigecycline
should be reduced to 25 mg every 12 hours—these patients
with severe liver dysfunction
96. • DISTRIBUTION- Concentrations at 4 hours after
tigecycline adminis tration were higher in
gallbladder (38-fold higher, n = 6), lung (8.6-fold
higher, n = 1), and colon (2.1-fold higher, n = 5),
and lower in synovial fluid (0.58-fold lower, n = 5)
and bone (0.35-fold lower, n = 6), relative to
serum.
• Cerebrospinal fluid penetration is low.
• Penetration into the urinary tract is probably
sufficient to defeat susceptible organisms.
97. Tetracyclines
• Tetracycline is a bacteriostatic antibiotic.
• doxycycline, minocycline, tetracycline.
TETRACYCLINE
• Tetracycline has broadspectrum activity against
bacteria,including cell wall–deficient organisms and
parasites, such as Plasmodia.
• Tetracycline remains an important agent in the therapy
of severe diarrhea due to Vibrio cholerae and in salvage
eradication regimens for Helicobacter pylori.
98. • Tetracycline remains an important agent in the
therapy of severe diarrhea due to Vibrio cholerae
and in salvage eradication regimens for
Helicobacter pylori.
• MOA: Tetracyclines inhibit bacterial protein
synthesis. They bind principally to the 30S
subunits of bacterial ribosomes and specifically
inhibit the enzyme binding of aminoacyltRNA to
the adjacent ribosomal acceptor site blocking the
elongation phase of protein synthesis.
99. • DOSAGE: The adult oral dosage is 250 mg
every 6 hours or 500 mg every 6 hours for
more serious infections.
• Intravenous preparations of tetracycline are
no longer marketed nor routinely available
because of fatal hepatoxicity reactions that
have accompanied their use
100. • Tetracycline is not recommended for use in
children AS IT CAUSES TEETH STAINING.
• Tetracycline should be avoided in patients
with renal failure as it may cause further
deterioration of renal function .
• Liver damage may occur as a complication of
highdosage tetracycline therapy.
101. Doxycycline
• Doxycycline is a second-generation
tetracycline with increased oral bioavailability
and tissue penetration as a result of its
improved lipophilicity compared with earlier
tetracyclines.
• Its mechanism of action is inhibition of
microbial protein synthesis through
interaction with 30S ribosomal subunits.
102. • doxycycline has a wide spectrum of activity but
the development of widespread bacterial
resistance and the development of other
bactericidal antibiotics has restricted its major
uses to the treatment of atypical, often
intracellular, bacterial pathogens as well as
malaria. Doxycycline is a crucial agent in the
therapy of Q fever, brucellosis, melioidosis,
“atypical” pneumonia, leptospirosis, and
rickettsial infections.
104. • Most of gram negative Enterobacteriaceae:
shigella; salmonella; proteus; klebsiella; E. coli;
enterobacter become resistant to tetracyclines.
• Yersinia pestis, against which doxycycline is the
mainstay of antimicrobial therapy, is a notable
exception among the Enterobacteriaceae.
• Brucella spp. are still uniformly doxycycline-
sensitive.
105. • MOA: Tetracyclines, including doxycycline, inhibit
bacterial protein synthesis through reversible
binding to the ribosomal complex.
• Apicoplast ribosomal subunits in P. falciparum
appear to be inhibited by doxycycline .
Doxycycline inhibition of protein synthesis in
these organelles prevents their replication, which
results in an antiparasitic effect in daughter
parasites that lack these organelles, thus
explaining the slow antimalarial effect of
doxycycline.
106. • DOSAGE: The adult dosage is 100 mg every 12
hours on day 1, then 100 mg every 12 hours for
severe infection, and 100 mg daily for less severe
disease.
• An i.v. preparation of doxycycline is available. The
adult dosage is 200 mg initially, followed by 100
mg every 12 hours. Each dose should be
dissolved in 500 or 1000 ml of glucose/ saline
fluid for slow i.v. infusion over a period of 0.5 to
1.0 hour.
107. • Doxycycline is safe in patients with renal
impairment.
• Although tetracyclines are excreted in bile,
this is not a major pathway in their excretion,
and patients with pre-existing liver damage do
not appear to be more prone to the toxic
effects of tetracyclines.
108. • Adverse Effects
• Gastrointestinal: Tetracyclines can cause esophageal
irritation, and patients should take the drug with water,
while standing up if possible. Tigecycline, though an IV
drug, can cause severe nausea, vomiting, and diarrhea.
• Dermatologic: Photosensitivity is often seen. Patients
should avoid the sun or use sunscreen while taking
tetracyclines.
• Sensory: Minocycline may cause dizziness and vertigo.
• Developmental: All tetracyclines can cause discoloration of
developing teeth and are contraindicated in pregnant
women and children younger than 8 years old
109.
110. ANAEROBES
• Anaerobes are predominant components of
the bacterial flora of the normal human skin
and mucous membranes, and are a common
cause of endogenous bacterial infections.
111. • The most commonly isolated antibiotic-
resistant anaerobes are those that belong to
the Bacteroides fragilis group.
112.
113. Nitroimidazoles: METRONIDAZOLE
• Spectrum: metronidazole
• Good: Gram-negative and Gram-positive
anaerobes, including Bacteroides, Fusobacterium,
and Clostridium species; protozoa, including
Trichomonas, Entamoeba, and Giardia
• Moderate: Helicobacter pylori
• Poor: aerobic anything, anaerobes that reside in
the mouth (Peptostreptococcus, Actinomyces,
Propionibacterium)
114. • Mechanism of Action:
Anaerobic bacteria and protozoa—but not aerobic
bacteria—activate a part of the nitroimidazole molecule
that forms free radicals, which are thought to damage DNA
and lead to cell death.
Adverse Effects
Gastrointestinal: Nausea, vomiting, and diarrhea, along with a
metallic taste, are not uncommon with metronidazole.
More severe adverse reactions such as hepatitis and
pancreatitis are rare.
Neurologic: Dose-related, reversible peripheral neuropathy
115. DOSAGE
• The adult dosage for treatment of anaerobic
infections is 400 or 500 mg three times daily.
• Metronidazole solution (500 mg in 100 ml)
should be infused intravenously at a rate of 25
mg or 5 ml per minute.
• The pharmacokinetics of metronidazole are
not significantly altered in patients with renal
impairment, and dosage adjustment is not
usually necessary.
