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- are compounds that destroys pathogenic microorganism or inhibit their growth- one of the most
valuable method of treating infection - most common agents used are:
o Antibiotics
o microbial products or their derivatives that are capable of killing susceptible
microorganism or inhibiting their growth.
ANTIBIOTICS
- chemical substances produced by bacteria, fungi, actinomyces that suppress the growth of
other microorganisms and may destroy them, e.g. penicillin, streptomycin, etc. Antimicrobial
compounds include synthetic compounds, e.g. quinolones, sulfonamides
- Are chemical substance produced by various species of microorganisms that are capable in
small concentrations of inhibiting the growth of other microorganisms.
- some are semi-synthetic in which the natural active component in the molecule is combined
with a synthetic group
- these substances functions to limit microbial growth by killing or inhibiting their growth
- Medications used to treat bacterial infections Ideally, before beginning antibiotic therapy,
Ideally, before beginning antibiotic therapy, the suspected areas of infection should be the
suspected areas of infection should be cultured to identify the causative organism cultured to
identify the causative organism and potential antibiotic susceptibilities.
chemical substances produced by bacteria, fungi, actinomyces that suppress the growth of
other microorganisms and may destroy them, e.g. penicillin, streptomycin, etc. Antimicrobial
compounds include synthetic compounds, e.g. quinolones, sulfonamides.
Antibiotics inhibit selectively the enzymes required for synthesis of acid, mammals use
preformed folic acid. 3.
Antibiotics selectively inhibit protein synthesis in bacteria which have 70S ribosomes,
whereas mammals have 80S ribosomes
Classification of antimicrobials
1. According to spectrum of activity a. Broad spectrum:
a.
Primarily bacteriostatic:
inhibit growth of organisms: e.g., sulfonamides, etc; and body’s immune system eliminates
the pathogens, if antimicrobial is stopped before the bacteria is destroyed, relapse may occur.
Not used in immunocompromised patients or in life threatening infections.
b.
Primarily bactericidal:
kill microorganisms; e.g.
β
-lactams, quinolones, etc. Use in the treatment of meningitis, endocarditis, and to treat
bacteremia in neutropenic patients. Bactericidals are divided into:
i.
β
lactams and vancomycin.
ANTIBIOTICS
I. Mechanism of Action (MOA) – directed against unique targets not present in mammalian cells
Goal: limit toxicity to the host & maximize chemotherapeutic activity affecting invading microbes only.
Bactericidal drug – kill bacteria within it’s spectrum of activity
Bacteriostatic drug – inhibit bacterial growth
(Refer Basic Antibacterial Mechanism of Action Table 118-1, page 790 depicted on Figure 118-1, page 791, or review pharmacology handouts of Dra.
Villar)
Chemotherapeutic Agents
- are compounds that destroys pathogenic microorganism or inhibit their growth- one of the most
valuable method of treating infection - most common agents used are:
> Antibiotics
> microbial products or their derivatives that are capable of killing susceptible microorganism or
inhibiting their growth
Antibiotics:
Antibiotics
Are chemical substance produced by various species of microorganisms that are capable in
small concentrations of inhibiting the growth of other microorganisms
A ntibiotic producing organisms:
some are semi-synthetic in which the natural active component in the molecule is combined
with a synthetic group
these substances functions to limit microbial growth by killing or inhibiting their growth
New definition: a substance produced by a microorganism or to a similar substance produced
Bacteria Bacillus Streptomyces Fungi Penicillium
• disrupts proteins or enzymes within a bacterium.
bacteriostatic – prevents multiplication
bactericidal – kills bacteria
Goal : limit toxicity to the host & maximize chemotherapeutic activity affecting invading microbes only.
Bactericidal drug – kill bacteria within it’s spectrum of activity
• Bacteriostatic drug – inhibit bacterial growth
Antibiotic resistance:
• bacteria mutate that they become resistant to certain antibiotics.
• common in nosocomial infections
• cause: indiscriminate antibiotic use
Cross – resistance
• resistance that occurs bw antibacterials with similar actions.
Classes of Antibiotics:
I. Aminoglycosides
gentamicin (Garamycin)
• amikacin
• neomycin
• tobramycin
• streptomycin
• Kanamycin
Monitor for:
nausea & anorexia
ototoxicity
nephrotoxicity
neurotoxicity
BM depression & superinfections
II. Cephalosporins
cefaclor (Ceclor)
Indications: Tx of respiratory, dermatological, urinary tract & middle ear infections
Monitor for:
GI upsets & diarrhea
Pseudomembranous colitis
headache, dizziness
nephrotoxicity
superinfections & bone marrow suppression
hypersensitivity reactions
b. 1st generation
• cephalexin (Keflex)
• cefazolin (Zolicef)
Indications: same as gram – positive bacteria affected by Pen G & gram – negative bacteria
( Proteus mirabilis, E. coli, & Klebsiella pneumoniae) PEcK
c. 2nd generation
• cefaclor
• cefuroxime ( Zinacef)
• cefoxitin
d. 3rd generation
• ceftazidime
• ceftriaxone (Rocephin)
• ceftizoxime
Indications: more potent against gram- negative bacilli as well as Serratia marcescens
(HENPEcKS)
e. 4th generation
• cefepime
• ceftditoren
Indications: for gram – negative & gram – positive organisms including P. aeroginosa
III. Fluoroquinolones
ciprofloxacin (Cipro)
• levofloxacin
• norfloxacin
• ofloxacin
• gatifloxacin
Indications: Tx of respiratory, skin, urinary tract, eye, ear, bone & joint infections.
Tx after anthrax exposure, typhoid fever
Action: inhibit synthesis of bacterial RNA & DNA in wide spectrum of gram – negative bacteria
Monitor for:
headache, dizziness
GI upsets
BM depression CI in children < 18 yo
risk of photosensitivity
IV. Macrolides
erythromycin
• azithromycin (Zithromax)
• clarithromycin
Monitor for:
nausea & vomiting, diarrhea, risk for pseudomonas colitis
hepatotoxicity
ototoxicty
V. Lincosamides
clindamycin
• lincomycin
Monitor for:
severe pseudomembranous colitis
BM depression
pain
Monitor for:
mild GI problems
liver toxicity
pain
Monitor for:
GI effects
superinfections
hypersensitivity reactions
VIII. Sulfonamides
sulfasalazine
• sulfadiazine
• cotrimoxazole
Action: blocks cellular metabolism of PABA for folic acid synthesis of susceptible gram-
positive & gram-negative baceria (bacteriostatic)
Monitor for:
hepatotoxicity
nephrotoxicity
Stevens- Johnson syndrome
CNS effects & BM depression
IX. Tetracyclines
tetracycline
• doxyclcine
• minocycline
Monitor for:
damage teeth & bones
GI effects
BM suppression, photosensitivity & superinfections
make oral contraceptives ineffective
X. Antituberculosis drugs
a. 1st line drugs
isoniazid (INH)
• rifampin
• ethionamide
• rifapentine
Monitor for:
discoloration of body fluids
hepatotoxicity
peripheral neuritis
The development of vaccine and antimicrobial agent that prevent and cure bacterial infections was one of the
twentieth century’s major contributions to human longevidity and quality of life.
Antimicrobial agent are among the most commonly prescribed drugs, however their indiscriminate use drives
up the cost of health care, leads to a plethora of side effect & drug interactions, and fosters the emergence of
bacterial resistance.
I. Mechanism of Action (MOA) – directed against unique targets not present in mammalian cells
Goal: limit toxicity to the host & maximize chemotherapeutic activity affecting invading microbes only.
Bactericidal drug – kill bacteria within it’s spectrum of activity
Bacteriostatic drug – inhibit bacterial growth
(Refer Basic Antibacterial Mechanism of Action Table 118-1, page 790 depicted on Figure 118-1, page 791, or
review pharmacology handouts of Dra. Villar)
C. Inhibition of Bacterial Metabolism (Antimetabolite – synthetic compound that interfere with bacterial
synthesis of folic acid which lead to the cessation of bacterial cell growth and to bacterial cell death).
• Sulfonamides – are structural analogues of p-aminobenzoic acid (PABA), one of the three structural
component of folic acid (the two are pteridine & glutamate), which competes with PABA for the enzyme
dihydropteroic acid synthetase which is responsible for the first step of folic acid synthesis.
• Trimethoprim – is a diaminopyrimidine, a structural analogue of the pteridine moiety of folic acid, which
serve as a competitive inhibitor of dihydrofolate reductase, an enzyme responsible for the reduction of
dihydrofolic acid to tetrafolic acid – the essential final component of folic acid synthesis.
D. Inhibition of Nucleic Acid Synthesis or Activity – cause disparate effect to nucleic acid
• Quinolones (including Nalidixic acid & its fluorinated derivatives [ciprofloxacin, levofloxacin, gatifloxacin &
moxifloxacin]) – synthetic compounds that inhibit the activity of the A subunit of the bacterial enzyme DNA
gyrase & topoisomerase IV, an enzyme responsible for negative supercoiling of the DNA – an essential
conformation for DNA replication in the intact cell (so walang DNA replication).
• Novobiocin – also interfere with the activity of DNA gyrase, but it interferes with the B subunit.
• Rifampicin – used primarily in M. tuberculosis. It binds tightly to the B subunit of bacterial DNA-dependent
RNA polymerase, thus inhibiting transcription of DNA to RNA.
• Nitrofurantoin – synthetic compound containing a single five-membered ring & it is reduced by bacterial
enzyme to highly reactive, short lived intermediates that are thought to cause DNA strand breakage.
• Metronidazole –a synthetic imidazole which is active against a wide range of anaerobic bacteria & protozoa, .
Its activity is totally dependent on its anaerobic electron-transport system for energy production, wherein the
nitro group of metronidazole is reduced to series of transiently produced, reactive intermediates that are
thought to cause DNA damage (maybe mutagenic & radiosensitizer of hypoxic mammalian cell).
A. Beta-lactam Resistance
• Destruction of drug by B-lactamase of gram-negative bacteria, which is confined in its periplasm , between
the inner & outer membranes, while in gram-positive bacteria secrete their B-lactamase into the surrounding
medium.
Strategy: combine B-lactam with an inhibitor (clvulanic acid, sulbactam & tazobactam) that avidly binds
the inactivating enzyme , preventing the attack on the antibiotics.
• Alteration of PBP targets so that the PBP’s have a markedly reduced affinity to the drug.
• Coupling, in gram-negative bacteria, of a decrease in outer-membrane permeability with rapid efflux of the
antibiotic from the periplasm to the cell exterior there is a mutation of gene encoding outer-membrane protein
channels called porins which decrease the entry of B-lactam into the cell, while additional protein form
channels that actively pump B-lactams out of the cell.
B. Vancomycin Resistance – the gene encoding resistance are carried on plasmids that can transfer themselves
from cell to cell and from transposons that could jump from plasmid to chromosomes. Resistance is mediated
by enzymes that substitute D-lactate for D-alanine on the peptidoglycan stem peptide so that there are no longer
an appropriate target for vancomycin binding.
C. Aminoglycoside Resistance
• Inactivation of the antibiotics by aminoglycoside modifying enzyme
• Decrease antibiotic uptake is some clinical isolate of P. aeruginosa presumably due to alterations in the
bacterial outer membrane
F. Tetracycline Resistance – due to plasmid encoded active-efflux pump that is inserted into the cytoplasmic
membrane & extrude antibiotic from the cell.
G. Topical Mupirocin Resistance – due to mutation of the target isoleucine tRNA synthetase so that it is no
longer inhibited by antibiotic or plasmid-encoded production of a form of the target enzyme that bind to
mupirocin poorly.
H. Trimethoprim & Sulfonamides Resistance -due to the acquisition of plasmid encoded genes to produce a
new, drug-insensitive target – insensitive dihydrofolate reductase for trimethoprim & an altered dihydropteroate
synthetase for sulfonamide.
I. Quinolones Resistance – due to the development of one or more mutations in target DNA gyrases and
topoisomerasesIV that prevent antibacterial agent from interfering with the activity of the enzyme.
J. Rifampin Resistance– due to developing mutation in the B subunit of RNA polymerase that render the
enzyme unable to bind the antibiotic.
III. Pharmacokinetics of Antibiotics – refers to concentrations in serum & tissue versus time & reflects the
process of absorption, distribution, metabolism & excretion.
Key terms: Peak & through serum concentration, half-life, clearance & distribution volume (alam nyo nay un
from pharma)
Pharmacodynamic Profile of Antibiotic – refers to the relationship between serum & tissue concentrations of
the antibiotic & its Minimal inhibitory concentration (MICs) for bacteria
A. Absorption – refer to the rate & extent of a drug’s systemic bioavailability after oral, IM & IV
administration,
1. Oral administration – it is usually used for patient with relatively mild infections in whom absorption is not
thought to be compromised by the preceeding conditions with varying bioavailability and has the advantage of
low cost, fewer adverse effect & greater acceptance to patient, however therapeutic efficacy may be
compromised when absorption is reduced as a result of physiologic or pathologicconditions, drug interactions or
noncompliance.
2. Intramuscular Administration – although route of administration result in 100%bioavailability, it is not
widely use due to pain of injection & the relative ease of IV access.
3. Intravenous Administration – appropriate whenoral antibacterial agents are not effective against a particular
pathogen, when bioavailability is uncertain,or when larger doses are required than are feasible with the oral
route.
B. Distribution – antibacterial agent must exceed the pathogen MICs & must distribute to the site of infection
to be effective. Hard to distribute areas are in the CSF, the eye, the prostate & infected cardiac vegetationwhich
require either high dose or local aministration for prolonged periods.
C. Metabolism & Elimination – by hepatic elimination & renal excretionof the unchanged or metabolized form,
or by a combination of the two processes.
Adustment of dosage of drug should be done when elimination capability is impaired as to prevent toxicity.
D. Site of Infection
• Meningitis – should received drugs that can cross the blood-CSF barrier & the agent must be
bactericidal due o the relative paucity of phagocytes & opsonins at the site of infection ex. Chloramphenicol
• Bacterial endocarditis vegetation – needs bactericidal, with the selected agent administered parentally
over a long period and at a dose that produces serum levels at least 8x higher than the minimal bactericidal
concentration (MBC)
• Osteomyolysis – site that is somewhat resistant to opsonophagocytic removal of infecting bacteria
• Chronic prostitis – difficut to cure because most antibiotics does not penetrate through the capillaries
serving the prostrate.
• Intraocular Infection (sp. endopthalmitis) – difficult to treat because retinal capillaries lacking
fenestration hinder drug penetration into the vitreous from blood.
• Abcess – poor penetration of antibiotics.
• Urinary Tract Infection (sp. in the bladder) – easy to cure because of higher concentration of antibiotics
to urine than in blood. (Nitrofurantoin & methenamnie salt)
E. Combination Therapy
Use of single agent therapy with a narrow spectrum of activity against the pathogen diminished the alteration of
the normal flora thus limiting the overgrowth of resistant nosocomial organism, avoids potential toxicity of
multiple-drug regimens & reduce the cost.
Circumstances for the Use of Multiple–drug regimen
1. Prevention of Emergence of resistant mutants – a second antibacterial agent with a mechnismof action
different from that of the first is added to prevent the emergence of resistant mutants.
2. Synergistic or Additive activity – involves the lowering of the MIC & MBC of each drugs tested in
combination against a specific bacterium. (Synergy – each agentis more active when combined with a second
drug than would be alone; Additive – combined activity of the drugs is equal to the sum of their individual
activities). Ex. B-lactam/Aminoglycoside & Trimethoprim/Sulfamethoxazole.
3. Therapy directed against multiple potential pathogens (ex. Intraabdominal or brain abcesses)
F. Empirical Theraphy
Antibacterial therapy is begun before a specific bacterial pathogens has been identified. Situations in which
empirical therapy is appropriate include the following:
1. Life threatening infection
2. Treatment of Community-acquired infections
A. B-lactam – Penicillins (except for the semisynthetic & penicillinase-resistant antistaphylococcal agents) are
ineffective against isolates procing B-lactamase enzymes.
• Penicillin G – spectrum including spirochete, streptococci, E. faecalis, most Neisseria sp., a few
staphylococcus, many fastidious oral bacteria, clostridium sp., Pasteurella multocida, Erysipelothrix
rhusiopathiae & Streptobacillus moniliformis.
• Ampicillin – extends the spectrum of penicillin G to some gram-negative rods active against some
isolates of E. coli, Proteus mirabilis, Salmonella, Shigella & H. influenzae.
• Penicillinase-Resistant Penicillins (ex. Methicillin) – use solely for the treatment of Staphylococcal
infection.
• Antipseudomonal Penicillin (ex. Piperacillin) – spectrum include bacteria covered by ampicillin as well
as some nonpseudomonal enteric gram-negative bacilli
• First-Generation Cephalosporin – spectrum including penicillinase-producing, methicillin-susceptible
staphylococci & streptococci but not a drug of choice of such infection. They have excellent activity against
many isolates of E. coli, Klebsiella pneumoniae & P. mirabilis & are among the drug of choice in
presumptive theraphy for community acquired pneumoniae.
• Parenteral Second-generation Cephalosporin (ex. Cefuroxime, Cefoxitin & cefotetan) – extends the
gram-negative spectrum of first generation compound with good activity against B. fragilis.
• Oral second- & third-generation Cephalosporin – have fair activities against gram-positive cocci & H.
influenzae & are widely used in patient with otitis media, sinusitis & lower respiratory tract infection.
• Third-generation parenteral cephalosporins (ex. Ceftaxidime & Cefepime) – all have broad spectrum of
activity against enteric gram-negative rods & are useful for treatment of hospital-acquired infection caused
by multiple resistant organism.
• Carbapenems (Imepenem, Meropenem, Ertapenem) – have excellent activity in vitro with virtually all
bacterial pathogens except Stenotrophomonas, MR Staphylococci & E. faecium. They are usually in
combination with renal dipeptidase inhibito cilastin to prevent renal inactivation.
• Monobactam (Aztreonam) – spectrum limited to gram-negative enteric bacilli.
B. Vancomycin – spectrum limited to gram-positive cocci, especially enterococci, streptococci & staphycocci
which serve as a second-line therapy for most gram-positve bacterial infection; drug of choice for
pseudomembranous colitis caused by C. deficille not responsive to metronidazole.
C. Aminoglycosides (Gentamicin & Tobramycin)– rapidly bactericidal in vitro at low concentrations, with
activity limited to gram-negative bacteria & staphylococci; drug of choice for any suspected gram-negative
bacteremia infection & for severe infection of the upper urinary tract. Streptomycin is the drug of choice in
initial therapy for tularemia, plague, glanders & brucellosis.
D. Macrolides (Erythromycin) & Ketolides – has a broad-spectrum activity against gram-positive bacteria with
the additional activity against (drug of choice)Legionella, Mycoplasma, Camphylobacter, Bordetella pertusis
and some Chlamydia isolates. Drug of choice to communit acquired pneumococcal pneumoniae & group A
streptococcal pharyngitis to penicillin-allergic patient. Clarithroymycin, in combination of proton pump
inhibitor has been the drug of choice for the treatment of gastric infection by H. pylori.
E. Lincosamides (Clindamycin) – shares gram-positve coccal spectrum of erythromycin but is more active
against susceptible staphylococci. Drug of choice for treatment of severe invasive group A streptococcal
infection.
F. Chloramphenicol – broad spectrum of activity against gram-positive & gram-negative bacteria, although
plasmid mediated resistance has diminished its effective spectrum. Remains the drug of choice for the
treatment of typhoid fever & plague & still useful for the treatment of brucellosis & both pneumococcal &
meningococcal meningitis in patient with severe penicillin allergy.
G. Tetracycline (Doxycycline & Minocycline) – has broad spectrum of bacteriostatic activity against gram-
positive & gram-negative bacteria & are widely used in a variety of community acquired infection. Drug of
choice for acute bacterial exacerbations of chronic bronchitis, granuloma inguinale, brucellosis, tularemia,
glanders, meliodosis, spirochetal infections caused by Borrelia, infectiondue to Vibrio vulnificus, some
Aeromonas infections due to Stenotrophomonas, plague, ehrlichiosis & due to Mycobacterium marinum.
H. Sulfonamides & Trimethoprim – has a broad spectrum of bacteriostatic activity individually & in
combination against facultative gram-negative bacteria & Staphylococci. Drug of choice for the treatment of
Nocardia Infections, Leprosy (dapsone) & toxoplasmosis (sulfadiazine), and uncomplicated urinary tract
infection.
I. Fluoroquinolones – excellent activity against most facultative gram-negative rods & variable activity against
gram-positive cocci. Oral agents with greatest activity to p. aeruginosa (Ciprofloxacon). Drug of choice for
urinary tract infection, bacterial gastroenteritis, community acquired pneumoniae & enteric fever & useful for
serious hospital-acquired infections caused by gram negative organism.
J. Rifampin – used for combination treatment of serious infection due to methicillin resistant staphylococci &
for chemoprophylaxis in persons at risk of meningococcemia meningitis & for treatment of Legionella
pneumonia.
K. Metronidazole – spectrum limited to anaerobic bacteria, specially gram-negative species (ex. Bacteroides
spp.). Drug of choice for the treatment of abscess in which the involvement of obligate anaerobes is suspected.,
treatment of bacteria vaginosis & antibiotic associated pseudomembranous colitis.
L. Linezolid – bacteriosttic spectrum limited to gram-positive bacteria & is indicated for the treatment of
infections caused by staphylococci, streptococci & enterococci.
M. Polymixins – broad spectrum of activity that includes virtually all gram-negative bacteria used commonly
as topical agent (ex. colistin).
O. Urinary Tract Antiseptics (Nitrofurantoin & Methenamine salt) – are active only in the lower urinary tract &
cannot be used as treatment for upper urinary tract or systemic infections, are most active against susceptible
gram-negative bacteria.
P. Topical Antibacterial Agents – mupuricin is available only as topical preparation for use against
staphylococci & streptococci, which has major application for impetigo & eradication of staphylococcal carrier
state.
VI. Adverse Reaction – mechanism of either dose-related (“toxic”) effects of unpredictable reactions
which is either idiosyncratic or allergic.
B. Vancomycin – most common side effect is the red man syndrome, characterized by pruritus,flushing &
erythema of the head & upper torso often mislabeled as allergy.
• Can rarely cause nephrotoxicity, ototoxicity, leucopenia, skin rashes & true allergy
C. Aminoglycoside – the two most common adverse reaction is nephrotoxicity (result from the accumulation
of aminoglycoside in the peritubular space, with damage to the proximal tubule & a corresponding reduction in
GFR) & Ototoxicity (auditory or vestibular damage since aminoglycoside can destroy hair cells in the inner
ear)
• Neuromuscular depression from aminoglycosides is caused by reduced acetylcholine activity at postsynaptic
membranes that can result in rare but severe respiratory depression.
D. Macrolides – Gastrointestinal effect such as burning, nausea & vomiting are the most common since
macrolides bind to motilin receptor, increasing gastrointestinal motility. Less common side effect is
hepatotoxicity & ototoxicity, and allergic cutaneous reaction.
E. Lincosamides – most common adverse effect is gastrointestinal distress ranging from diarrhea to
pseudomembranous colitis. Allergic reaction, hepatotoxicity & neutropenia are observed in only rarely.
F. Chloramphenicol – causes two types of bone marrow suppression: a dose-related, reversible suppression of
all elements which occur commonly during therapy at the maximal recommended dose, & an idiosyncratic,
irreversible aplastic anemia.
• In premature neonates & infants, it can cause dose-related “gray syndrome” characterized by cyanosis,
hypotension & death that results from an inability of the newborn to metabolize the drug.
G. Tetracyclines – GI effects (most common) which may be related to a direct irritant effect, since it could also
cause esophageal ulcerations when they dissolve before reaching the stomach..
• Hepatotoxicity has been reported after administration of tetracycline intravenously at a lower doses during
pregnancy, hence it is contraindicated in pregnant woman,
• Tetracyclines are contraindicated in children <8y/o because of mottling of the permanent teeth.
H. Sulfonamides & Trimethoprim – generally safe but may occasionally cause a number of allergic reactions,
from relative minor skin rashes to severe life threatening reactions such as erythma multiforme, steven Johnson
syndrome & toxic epidermal necrosis.
• Both can also cause severe hematologic complications, including agranulocytosis, hemolytic & megaloblastic
anemia & thrombocytopenia.
• Renal insufficiency, caused by crystals of the relatively insoluble acetyl metabolites, is observed primarily
with the long-acting sulfonamides.
• It is recommended that sulfonamides not be administered in the newborns because of concerns that bilirubin
may be displaced from protein-binding sites, with subsequent jaundice & kernicterus.
• Occasionaly could cause drug fever with serum sickness, hepatic toxicity & systemic lupus erythematosus.
I. Fluoroqunolones – are relatively safe but adverse reaction discontinuation of therapy which includes GI
distress, central nervous system effect including insomnia & dizziness. Phototoxiciy is occasionally severe .
Rarely hepatic & renal dysfunction & anaphylactoid & allergic reaction are observed.
J. Rifampin – is generally well-tolerated but has several important side effect such as transient rise in hepatic
aminotransferases although rifampin hepatitis is rare. Patient should also be warned that rifampin & its
metabolites cause secretions such as urine, tears, sweat & saliva to turn orange & that contact lens may be
stained.
K. Metronidazole – GI side effect such as nausea are most frequent but rarely necessitate discontinuation of
theraphy. A metallic taste is relatively common, & stomitis & glositis are occasionally reported
• Concerns about mutagenecity & carcinogenicity from metronidazole have led to recommendations that it
not be used in pregnancy when alternative agents are available.
L. Linezolid – GI upset (nausea, vomiting & diarrhea) & headache. Of most concern is a reversible
myelosuppresion that is directly related to the duration of theraphy.
M. Quinupristin/Dalfopristin –venous irritation is frequent & potential adverse effect when the drug is given by
peripheral intravenous infusion. In addition, arthralgia & myalgia are substantially more common among
patient treated with quinupristin/dalfopristin.
A. Macrolides & Ketolides – erythromycin, clarithromycin & telithromycin inhibit the p450 enzyme CYP3A4
& thus metabolism of other drugs, including cyclosporine, certain statins, theophylline, carbamazepine,
warfarin, certain antineoplastic agents & ergot alkaloids.
C. Linezolid – are monoamine oxidase inhibitor & its concomitant administration with sympathomimetics, with
SSRI & with food with high concentration of tyramine should be avoided
D. tetracycline – reduction in absorption when these drugs are coadministerd with divalent & trivalent cations
such as antacids, iron compounds or dairy products.
F. Fluoroquinolones – like tetracycline, are also chelated by divalent & trivalent cations. Certain
fluroquinolones including ciprofloxacin, inhibit hepatic enzymes that metabolized theophyllin, thus
theophylline toxicity.
G. Rifampin – an excellent inducer of many cytochrome P450 enzymes & increases the hepatic clearance of a
number of drugs including oral contraceptive, warfarin, cyclosporine & prednisone, & verapamil & diltiazem.
IX. Duration of Theraphy & Treatment (Refer to table 119-9, page 805)
• The ultimate test of cure for a bacterialinfection is the absence of relapse (the occurrence of infection with the
identical organism that cause the first infection.
• In general, the duration of the therapy should be long enough to prevent relapse yet not excessive that could
cause increase side effects of medication & encourage the selection of resistant microorganism
ZPDM 2005