NeelimaInhibitors of cell membrane function=Isoniazid ,Amphotericin BInhibitors of nucleic acid function or synthesis=Fluoroquinolones ,Rifampin
Combining bactericidal drugs may cause synergistic effect, especially with drugs with different mechanism of action, e.g. combination of penicillin with aminoglycosideresults in synergism against susceptibleE. coli, Klebsiella, Proteus, Pseudomonas
combination of ampicillin and clavulanic acid acts synergistically, the latter drug inhibiting beta lactamase production by the organism and thus protects penicillin,This occurs because penicillin helps in entry of aminoglycoside through microbial cell wall.
Therapeutic index=how safe the drug is?? High safetyClotrimoxazole when given c diurectics =THROMBOCYTOPENIA
Ans :d Elevated blood pressure would not be expected to markedly influence the type of antimicrobial treatment used.
Respiratory illness may beof viral origin. Furthermore, consequences of a chronic disorder may not warrant prophylactic use of antibiotics. Infection following implantation of a hip prosthesis is such a serious complication that prophylactic antibiotics are warranted.ans d
Correct answer = E. Giving a drug that exhibits concentration-dependent killing by once-a-day bolus infusion achieves high peak levels, favoring rapid killing of the infecting pathogen. The highly polar, polycationic structure of the aminoglycosides prevents adequate absorption after oral administration.Therefore, all aminoglycosides (except neomycin) must be given parenterally to achieve adequate serum levels.
Bacterial meningitis is a medical emergency that requires immediate diagnosis and treatment. Specimens for possible microbial identification must be obtained before drugs are administered whenever possible. Therapy should not be delayed until laboratory results are available
Rapidly absorbed and excreted ??? Sulfuoxazole,sulfamethaoxazole,sulfadiazine
1.The affinity of PABA with dihydrofolic acidsynthetase(DHFA) is 5000-15000 times more strongly than that of sulfonamides, 2. Sulfonamide resistance may occur as a result of mutations that cause overproduction of PABA, cause production of a folic acid synthesizing enzyme that has low affinity for sulfonamides, or cause a loss of permeabilityto the sulfonamide
Inhibit metabolism of warfarin,phenytoin&tolbutamideIncrease in methotrexate toxicity
Primarily active against ??????????????????????????gram –ve
Ciprooxacin is the drug of choice for postexposure prophylaxis and for treatment of anthrax. Alternateagents include doxycycline (mcq)
Cross placenta & conc in amniotic fluid
1.Levofloxacin is often effective in treating infections unresponsive to β-lactam antibiotics, such as amoxacillin-clavulanic acid.2.Levofloxacin and moxioflxacin are known as “respiratory fluoroquinolones” due to their activity versus Streptococcus pneumoniae.3.Ciprooxacin is highly ecacious in treating acute diarrheal illnesses due to enteric pathogens.
High photosensitivity-sparfloxacinMoxifloxacin – QT interval prolongation
Prophylaxis with cotrimoxazole is the standard treatment for patients with human immunodeficiency virus with CD4+ counts at 200 cells/mm3 or lower. Trimethoprim and sulfamethoxazole are not effective as monotherapy. It can be used in combination with dapsone. Clindamycin is effective in pneumonia, which has already developed due to this organism, but is not used prophylactically because of its adverse effect on the gastrointestinal tract. Ciprofloxacin lacks activity against this organism.ans c
Correct answer = D. Levofloxacin, a third-generation fluoroquinolone, shows increased activity against both gonorrheal and chlamydial infections compared to the second-generation examples, ciprofloxacin and norfloxacin. Nalidixic acid, a first-generation fluoroquinolone, lacks activity in these conditions. Moxifloxacin, a fourth-generation fluoroqinolone, also does not affect these atypical organisms.
Ciprofloxacin does not have sufficient activity against S. pneumoniae to be effective. Because it is not a β-lactam, ciprofloxacin is effective in treating UTIs caused by β-lactamase producing organisms
Increased release of albumin bound bilirubin increases the plasma concentration of free bilirubin, which can penetrate the central nervous system
Carboxy active against p.aerogenosa, piperacillin 8 times more active against pseudomonasThe antibacterial effects of all β-lactam antibiotics are synergistic with the aminoglycosides
Pseudomonas ????????????????????– ciprofloxacin,piperacillian,carboxy-carbenecillin/notgiven orally ,ticarcillin,ceftazidine,cefperazone,cefipime&other 3rd gen cephlosporins,,,duration of action 28 days …
Drugs not given iv???????Paracetamol,diclofenac,chlorquine,adrenaline
Prophylactic use –SABE,R.fever,Agranulocytosis pt
Methicillinresistant Staphylococcus aureus (MRSA) is currently a source of serious community and nosocomial (hospital-acquired) infections and is resistant to all commercially available β-lactam antibiotics, including antistaphylococcalpenicillins. This organism is usually susceptible to glycopeptidevancomycin. The penicillinase-resistant penicillinshave no activity versus gram-negative infections
Ampicillin (with or without the addition of gentamicin) is the drug of choice for the gram-positive bacillus Listeriamonocytogenes and susceptible Enterococcal species. These extended-spectrum agents are also widely used in the treatment of respiratory infections, and amoxicillin is employed prophylacticallyby dentists for patients with abnormal heart valves who are to undergo extensive oral surgery
Doesn’t undergo metabolism in body except cefotaxime (3rd gen ) partially metabolised in liver. Excreted by kidney exception Cefperazone /biliary excretion .
ceftriaxone or cefotaxime is effective in the treatment of neonatal and childhood meningitis caused by H. influenzae.
Due to overuse nosocomialenterococci- notably resistant
Compounding the imipenem with cilastatin protects the parent drug and, thus, prevents the formation of the toxic metabolite.Meropenem, ertapenem, and doripenem do not require co-administration of cilistatin. Ertapenem can be administered via IV or IM injection once daily
Aztreonam [az-TREE-oh-nam], which is the only commercially available monobactam, has antimicrobial activity directed primarilyagainst the Enterobacteriaceae, including P. aeruginosa. safe alternative for treating patients who are allergic and unable to tolerate penicillinsand/or cephalosporins.
Inactivation occurs if mixed c pencillin ????mcqnotadmins together
Antimicrobial spectrum gram +vecocci&bacilli,gram-vecocci & bacilli,chlamydia,mycoplasma,treponema&helicobacter….
Di-demeclocylineanatagonise ADH action & reduce urine conc ability of kidney ….
Advantages of doxy over tetraLonger half life,Less chance of GI disturbance,Better GI distribution,High lipid solubility
Doc for treating typhoid previously ,not used now
Treatment includes tobramycinalone or in combination with anantipseudomonal penicillin, such as piperacillin or ticarcillin in immunocompromised patients, and in burn victims. INFECTIONS DUE TO ENTEROCOCCI-Recommended therapy is with gentamicin or streptomycin plus vancomycin or a β-lactam,such as ampicillin.
Less ototoxicity -netilmycin
Mycobacteria are intrinsically resistant to most antibiotics.They grow slowly compared with other bacteria, antibiotics that are most active against growing cells are relatively ineffective. so, that’s why we use cobination of drugs.Mycobacterial cells can also be dormant and thus completely resistant to many drugs or killed only very slowly.
Isoniazid and Rifampin are the two most active drugsTo prevent resistance atleast 2 drugs used
Safest drug in pregnancy – INH,EthambutolInethambutol toxicity red &green vision defect seenDrug penetrating into caseous necrosis in TB -rifampicin
Anti Tn drug CI in pregnancy - Streptomycin
rifampin and clofazimine –antiinflmm,immunosupressantDapsone-lepraereaxn/ag-abreaxn/DOC rifampicinSteroid supress collagen wound healing delayed so not used…
1. Paul ehrlich??????
MBC is the lowest concentration of antibiotic that
kills 99.9 percent of bacteria
6. Mechanisms of action of
1. Inhibition of cell wall
1.Penicillins, cephalosporins, bac
2. leakage of the cytoplasmic
3. Inhibition of protein synthesis
&impairment of function of
4. Interference in
5. Antimetabolite actions :
6. Binding to viral enzymes
essential for DNA synthesis
2.Polymixin, collistin, polyene, a
antibiotics, and clindamycin
6.Vidarabine and acyclovir
New infection occurring during antimicrobial treatment
for another infection.
Assoc c broad /extended spectrum antibiotics such as
tetracycline ,chloramphenicol,ampicillin ,newer
1. Pt on CS therapy
2. AIDS pt
3. SLE & DLE
4. Leukemia & other malignancies
5. Autoimmune disorders (MM,MG)
Clostridium difficile treatment result in
pseduomembraneous colitis due to treatment with
Resistant Staph enteritis due to treatment c cloxacillin
& its congeners.
Candida albicans result in oral thrush.
Proteus treatment result in UTI
Diarrhoea due to treatment c tetracycline
9. Combined use of drugs
To prevent drug resistance
To obtain synergism
To dec adverse effects
To broaden spectrum of activity
1.2 static drusgs combined – additive effect
2.2 cidal drugs combined – additive only if bact sensitive to both
3.Cidal + static =??
If bact sensitive to static drug =synergism
If bact sensitive to cidal drug =antagonism
10. Adverse effects
Local toxicity – thrombophebitis
Systemic –c high therapeutic index
-c low therapeutic index (not safe)
- c very low
eg: polymyxin,vancomycin,amphotericin B
Which one of the following patients is least likely to
require antimicrobial treatment tailored to the
A. Patient undergoing cancer chemotherapy.
B. Patient with kidney disease.
C. Elderly patient.
D. Patient with hypertension.
E. Patient with liver disease.
In which one of the following clinical situations is the
prophylactic use of antibiotics not warranted?
A. Prevention of meningitis among individuals in close
contact with infected patients.
B. Patient with a hip prosthesis who is having a tooth
C. Presurgical treatment for implantation of a hip
D. Patient who complains of frequent respiratory illness.
E. Presurgical treatment in gastrointestinal procedures.
Which one of the following is the best route of
administration and dosing schedule for treatment with
aminoglycosides based on the drug’s
concentrationdependent killing property?
A. Oral every 8 hours.
B. Oral every 24 hours.
C. Parenterally by continuous intravenous infusion.
D. Parenterally every 8 hours.
E. Parenterally every 24 hours.
A 57-year-old man complains of
fever, headache,confusion, aversion to light, and neck
rigidity. A presumptive diagnosis of bacterial meningitis is
made.Antimicrobial therapy should be initiated after
which one of the following occurrences?
A. Fever is reduced with antipyretic drugs.
B. Sample of blood and cerebrospinal fluid have been taken.
C. A Gram stain has been performed.
D. The results of antibacterial drug susceptibilitytests are
E. Infecting organism(s) have been identified by the
First antibiotic to treat pyogenic infections .These agents are bacteristatic; and
get inactivated by presence of pus. Also called sulfa drugs.
1.Short Acting Sulfonamide:4-6hr
a. Sulfadiazine /orally given
2.Intermediate Acting Sulfonamide:8-12hr
3.Long Acting Sulfonamide:7 days
4. Special sulfonamides
for local application:
a. Mafenide-used in burns
b. Silver sulfadiazine –used in burns
c. Sulacetamide- ophthalmic use
for GIT disturbance:
a. Phthalyl sulfathiazole
b. Sulfasalazine-antidiarrhoeal/poorly absorbed from gut
Used rarely alone ;in combi c trimethprim
(STD)Earlier used in treatment of typhoid.
Ocular sulfacetamide sodium –bact ocular infn
Sulfamethopyrazine&Sulfadoxine used c
pyrimethamine for chloroquine intolerant malaria.
Folic acid is donor for DNA synthesis,This reaction takes place in
bacteria & humans
inhibitFolate synthetase (blocked by
Folate reducatse (blocked by trimethoprim)
18. Adverse reactions
1.Urinary Tract Disturbances
Sulfonamides may precipitate in urine producing crystalluria, hematuria or
even obstruction.(acetylated metabolites )/mcq
Crystalluria is treated by administration of sodium bicarbonate to alkalinize the
2. Hematopoietic Disturbances
Sulfonamides can cause hemolytic or aplastic anemia (Blood dyscrasias).
May provoke hemolytic reactions in patients whose red cells are deficient in
5.Bm toxicity in elderly pt
6.Kernicterus in newborns. (trimethoprim)displace bilirubin from protein
binding,free bilirubin deposit in basal ganglia & thalamus /mcq
Naladixic acid is the predecessor to all
fluorinated quinolones (FQs) represent a major
Quinolones are rapidly bactericidal drugs
«Broad spectrum of activity
«Improved PK properties – excellent
bioavailability, tissue penetration, prolonged half-lives
Disadvantages: resistance, expensive
Inhibiting bacterial topoisomerase (DNA gyrase) and
topoisomerase IV, block bacterial DNA synthesis and
put bacteria to death.
23. Mechanisms of Resistance
Altered target sites – chromosomal mutations in genes
that code for DNA gyrase or topoisomerase IV
«most important and most common
Altered cell wall permeability –decreased porin
Expression of active efflux – transfers FQs out of cell
Cross-resistance occurs between FQs
Ofloxacin, enoxacin and lomefloxacin are almost
completely absorbed orally; norfloxacin is 35-45%;
ciprofloxacin is 67% orally absorbed.
The FQs are widely distributed in body fluids and
tissues , The concentrations in
prostate,kidney, neutrophils, and macrophages exceed
serum concentrations, but in the cerebrospinal fluid
Most FQs are elimiated by renal mechanisms;therefore
the dosage must be adjusted according to renal fn
25. Norfloxacin is the least active of FQs against both gram-
negative and gram-positive organisms.
Ciprofloxacin is the most active agent against gramnegatives, P.aeruginosa in particular.
Levofloxacin, the L-isomer of ofloxacin and twice as
potent, has superior activity against gram-positive
organisms, including S. pneumoniae.
Methicillin-susceptible strains of S. aureus are generally
susceptible to FQs, but methicillin-resistant strains of
staphylococci are often resistant.
Pneumococci and streptococci of group are resistant to
In general, Penicillins and cephalosporins are more active
than FQs against streptococci and staphylococci
Urinary tract infections:FQs are effective for
uncomplicated and complicated UTI even when caused by
Ciprofloxacin and ofloxacin are effective forgonococcal
Ofloxacin is effective for chlamydial urethritis or cervicitis.
Intestinal tract infections:
effective for intraabdominal infections and bacterial
diarrhea caused by shigella, salmonella, E. coli, or
Respiratory tract infections:Not been routinely
recommended for treatment of pneumonia and other
upper respiratory tract infections.These
infections, predominantly caused by pneumococci and
streptococci, are usually well treated with betalactams or
However, levofloxacin, sparfloxacin, and newer FQs with
enhanced G+ activity and activity against
atypicalpneumonia pathogens (e.g.
chlamydia, mycoplasma, and legionella) are likely to be
effective and used increasingly for treatment of upper and
lower respiratory tract infections
28. Infections of the bones, joints, skin and soft
tissues:Including those caused by multidrug-resistant
organisms such as pseudomonas and enterobacter.
6. Others: Ciprofloxacin or ofloxacin is occasionally
used for treatment of tuberculosis and atypical
Ciprofloxacin is also a second-line agent for
29. Adverse effects
1.Gastrointestinal upsets (the most
common)Nausea, vomiting, diarrhea, dyspepsia
2.Allergy and anaphylaxis
3.Central Nervous System (1~7%)
Headache, agitation, insomnia, dizziness, rarely,
hallucinations and seizures (rarely)
4.Possibly damage to growing cartilage: NOT recommended
for patients younger than 14 years old, pregnant or nursing
5.Concomitant administration of theophylline and
quinolones can lead to elevated levels of theophylline with
the risk of toxic effect, especially seizure.
A 30-year-old male is diagnosed to be human
immunodeficiency virus (HIV) positive. His CD4+ count is
200 cells/mm3 and his viral load is 10,000 copies/mL. In
addition to receiving antiviral therapy, which of the
following is indicated to protect him against pneumonia
due to Pneumocystis jiroveci?
A 26-year-old young man presents with the symptoms
of gonorrhea. Because this condition is often
associated with an infection due to Chlamydia
trachomatis,which of the following quinolones would
be the best choice for treating him?
B. Nalidixic acid.
In which one of the following infections is
A. Urinary tract infections due to a β-lactamase
producing strain of Klebsiella.
B. Pneumonia due to Streptococcus pneumoniae.
C. Exacerbation of chronic bronchitis due to Moraxella
D. Urinary tract infection due to Escherichia coli.
E. Urinary tract infection due to Pseudomonas
Sulfonamides increase the risk of neonatal
A. Diminish the production of plasma albumin.
B. Increase the turnover of red blood cells.
C. Inhibit the metabolism of bilirubin.
D. Compete for bilirubin-binding sites on plasma
E. Depress the bone marrow.
35. Pencillin G or benzyl pencillin
Mold Penicillium chrysogenum.
Food interfere c absorbtion,get destroyed by gastric acid
,oral route not given
Anaphylaxsis seen SCRATCH test
Jarisch – Hexeimer reaction – seen in syphilis
pt,spirochetes release lytic products react c pencillin
Fever ,myalgia,rashes,angioedema noted
Type of pencillin
2. Benzathine pencillin
3. Crystalline pencillin
4. Pencillin V
Prodrug is becampicillian ,well absorbed orally
Act by inhibiting transpeptidase ..(mcq)
Incomplete oral absorbtion, food interferes; so interfere c
metabolism of other drugs
eg:OCpills,Hydrocortisone & pencillin not mixed in same
syringe as hydrocortisone inhibit action of pencillin,
allupurinol INC rashes by ampicillin,
prebenecin retards excretion by competing cfor tubular
Superinfection common,frequent diarrhoea after oral.
Lesser incidence of skin rashes & diarrhoea
compared to ampicillin
Pencillin DOC in
4. St infn
40. β lactamase inhibitor
After binding to βlactamase get inactivated called
Combi c amoxycillin called coamoxiclav
Progressive, after binding to βlactamase get
Combi c ampicillian called Sulficillin
41. Generation Effective against Ineffective
Gram +ve & -ve
Broad gram –ve
&Some gram +ve
Similar to gen 3
but more effective
42. Cephalosporium C
same mode of action as penicillins
tend to be more resistant than the penicillins to
Addition of side chain to position 7 of βlactum ring
alter spectrum of activity
Addition of side chain to position 3 of dihydrothiazine
ring alter pharmacokinetics
43. Adverse effects
Diarrhoea & maculopapular rash-most common
Nephrotoxicity (highest c Cephaloridine)
Bleeding due to hypoprothrombinaemia (seen in
Neutropenia& thrombocytopenia –Ceftazimide
Disulfiram like reaction c alcohol–
44. Other βlactamases
Carbapenems are synthetic β-lactam antibiotics that
differ in structure from the penicillins
Broad spectrum activity
Used in combi c Cilastatin , which prevents its rapid
hydrlysis at renal tubular cells
Azotreonam- βlactam in which other ring s missing
lacks cross sensitivity so promising in pt c pencillin
An elderly diabetic patient is admitted to the hospital with
pneumonia. The sputum culture stains for a gram-negative
rod. The patient is started on IV ampicillin.Two days
later, the patient is not improving, and the microbiology
laboratory reports the organism to be a β-lactamase
producing H. influenzae.
What course of treatment is indicated?
A. Continue with the IV ampicillin.
B. Switch to IV cefotaxime.
C. Switch to oral vancomycin.
D. Add gentamicin to the ampicillin therapy
A 70-year-old alcoholic male with poor dental hygiene is to
have his remaining teeth extracted for subsequent
dentures. He has mitral valve stenosis with mild cardiac
insufficiency and is being treatedwith
captopril, digoxin, and furosemide. The dentist decides
that his medical history warrants prophylactic antibiotic
therapy prior to the procedure and prescribes which of the
A patient with degenerative joint disease is to undergo
insertion of a hip prosthesis. To avoid complications due to
postoperative infection, the surgeon will pretreat this
patient with an antibiotic. This hospital has a significant
problem with MRSA. Which of the following antibiotics
should the surgeon select?
A 25-year-old male returns home from a holiday in the
Far East and complains of 3 days of dysuria and a
purulent urethral discharge. You diagnose this to be a
case of gonorrhea. Which of the following is
A. Ceftriaxone IM.
B. Penicillin G IM.
C. Gentamicin IM.
D. Piperacillin/tazobactam IV.
E. Vancomycin IV.
51. Broad spectrum
Gp1&2 not absorbed orally(1/2-2hrbefore food) ,food
interferesbut gp3 are well absorbed orally & widely
52. MOA-act by inhibiting protein synthesis by binding to 30S
Absorbed better in empty stomach
Conc in liver spleen & bind to CT including bone
Intracellularly bind to mitochondria
Primarily excreted in urine( dose reduced in renal disease
except doxycycline )
Form insoluble complex c milk ,metal ion ,antacid , fe
prepn & cause toxicity forming CHELATE
Minocycline conc in fat
CI in pregnant & lactating mother.sec in breast milk
53. Adverse effects
Esophageal ulceration if material from doxycycline is
released in esophagus
Liver damage –acute hepatic necrosis in pregnant
Renal failure/FANCONI’s SYNDROME –produced by use
of oudated tetracycline resulting renal tubular necrosis;
acidosis result so bicarbonate given to neutralize it.
Phototoxicity/highest c demeclo&doxycycline
Vestibular toxicity – minocycline(ataxia,vertigo,nystgmus)
Superinfection – pseudomembraneous colitis
Brownish dicolouration of teeth- if midpregn&5mt EU
cycle,3 mo – 5 yr affect premanent ant teeth,late pregnancy
& childhood –supress bone growh
54. Conc in gingival crevice 2-10 times that in serum,widely
used in treatment of periodontal disease
It potentiates anticoagulant action of coumarin drugs
Avoided in infants & children upto 12 yr of age
tetracycline-250 mg qid
Minocycline-100 mg bid
Doxycycline -100mg od
Local drug delivery in PD pocket
first choice of drug in LGV,
rickketssial infn-Q fever/rocky mountain spotted
Obtained from st venezulae
Act by binding to 50s ribosome
Broad spectrum & bacteriostatic
Most common cause of BM depression causing aplastic
GRAY BABY SYNDROME-when given to neonates esp
premature infants .
Metabolised by glucoronide conjugation ;def results
57. Pneumonic tularemia results from infection by the
respiratory route or by bacteremic seeding of lungs.
Gentamicin is effective in treating this rare lymphoid
Not ototoxic –netilmycin
used as anti TB drug???
Most resistant to bact inactivating enzymeAMIKACIN
Macrolides are a class of antibiotics, the basis of the
chemical structure of which is macrocyclic lactone
Depending on the number of carbon atoms in the ring
16-membered (midecamycin, spiramycin, josamycin).
Mechanism of action
Inhibit protein synthesis by binding to the 50 s subunit
Low conc bacteriostatic,high concentration
Absorption incomplete but adequate from intestine
Inactivated by gastric HCL, hence given as :
Enteric coated tablets or ester (stearate, ethyl succinate )
Food delays absorption
Not metabolized and actively secreted in bile ( major
route of excretion
Widely distributed into most tissues, except the brain and
CSF ; Cross the placental barrier
Narrow antibacterial spectrum
Used as alternative to pencillin/allergic pts
(Staph.Aureus,S. pyogens, S.pneumoniae,T.pallidum)
Diphtheria & whooping cough – drug of choice
Legionnaires disease- drug of choice
Pneumoniae ( M. pneumoniae ) – children
Rapid oral absorbtion
Marked tissue distribution
Advantage over erythromycin & clarithromycin
Once daily dosing
No inhibition of cytochrome P- 450
Major problem –pseudomembraneous /c.difficle
Drug for treatment –metronidazole or vancomycin
63. Antitubercular drugs
64. Drugs Used in Tuberculosis
First-line drugs :
2. Isoniazid (INH),
4. Ethambutol, and
. DAPSONE & OTHER SULFONES:
used effectively in the long-term treatment of leprosy.
Mechanism of action :
Dapsone like the sulfonamides, inhibits folate
synthesis (PABA antagonist).
Clinical uses :
Tuberculoid leprosy: with rifampin
Lempromatous leprosy: with rifampin and clofazimine