Antibacterial agents
Traditional targets of antibacterial compounds
Nature Chemical Biology 3, 541 - 548 (2007)
Cell wall inhibitors
Introduction
• The cell wall of bacteria contains peptidoglycan, a
substance that does not occur in eukaryotes
• The Gram-positive cell wall is composed of a
thick, multilayered peptidoglycan sheath
outside of the cytoplasmic membrane
• The Gram-negative cell wall is composed of an
outer membrane linked by lipoproteins to thin,
mainly single-layered peptidoglycan
1. Beta lactam antibacterial
1.
2.
3.
4.
5.
Penicillins
Cephalosporins & Cephamycins
Carbapenems: imipenem
Monobactams: aztreonam
Beta-lactamase inhibitors: clavulanic acid
Mechanism of action
• All β-lactam antibiotics interfere with the synthesis of
the bacterial cell wall peptidoglycan
• β-Lactam antibiotics, structural analogs of the natural
D-Ala-D-Ala substrate, covalently bind to the active site
of PBPs
• They interfere with the last step of bacterial cell wall
synthesis (transpeptidation or cross-linkage)
• This results in cell lysis, either through osmotic pressure
or through the activation of autolysins
• β-Lactam antibiotics are thus bactericidal
Penicillins
• The penicillins are a large group of bactericidal
compounds
• They can be subdivided and classified by their
chemical structure and spectrum of activity
• The antibacterial spectrum is determined by
their ability to cross the bacterial
peptidoglycan cell wall to reach the PBPs in
the periplasmic space
Penicillins
• In general, gram-positive microorganisms, in
the absence of resistance, are susceptible to
penicillins
• Gram-negative microorganisms have an outer
lipopolysaccharide membrane (envelope)
surrounding the cell wall that presents a
barrier to the water-soluble penicillins
Penicillins
• The antimicrobial activity of penicillin resides
in the β-lactam ring
Splitting of the β-lactam ring by either acid
hydrolysis or β-lactamases results in the
formation of penicilloic acid, a product without
antibiotic activity
Penicillins may be classified into four
groups:
1) Natural penicillins (G and V)
2) Antistaphylococcal penicillins
3) Extended-spectrum penicillins
4) Antipseudomonal penicillins
I. Natural Penicillins
• Are obtained from fermentations of the mold Penicillium
chrysogenum
• The have limited spectrum of antibacterial activity and
susceptible to beta-lactmase
• Clinical uses include treatment of infection caused by a
number of gram positive and gram-negative cocci,
gram-positive bacilli, , and spirochetes
• Most strains Staphyloccus aureus and significant number
of Neiseria gonorrhoea are resistant
• Penicillin G is the DOC for syphilis
I. Natural Penicillins
• Penicillin G: is an acid-labile compound & is most
appropriate for IM or IV therapy
• Penicillin G is excreted by the kidneys, with 90% of renal
elimination occurring via tubular secretion
• Probenecid blocks tubular secretion and has been used to
increase the serum concentration and prolong its half-life
of penicillin
• Depot IM formulations of penicillin G, including
procaine penicillin and benzathine penicillin, have
decreased solubility, delayed absorption, and a prolonged
half-life
I. Natural Penicillins
• Penicillin V:
• An oral formulation that resists degradation by
gastric acid .
• Antibacterial spectrum of activity is similar to that
of penicillin G
• Penicillin V is used to treat streptococcal
infections when oral therapy is appropriate and
desirable
II. Antisatphylococcal penicillins
• Agents: Methicillin, nafcillin (IV), oxacillin,
• Are more resistant to bacterial β-lactamases than is
penicillin G
• Their use is restricted to the treatment of infections known
or suspected staphylococcal infections
• Methicillin resistant S aureus (MRSA) and S epidermidis
(MRSE) are resistant
• They are active against staphylococci and streptococci
but not against enterococci, anaerobic bacteria, and
gram-negative cocci and rods.
III. Extended-spectrum penicillins
• Agents: Ampicillin and amoxicillin
• Antibacterial spectrum similar to that of
penicillin G more effective against gramnegative bacilli, but remains susceptible to
penicillinases
Ampicillin:
a) Treatment of meningitis caused by Listeria
monocytogenes.
b) Enterococcal endocarditis
c) Pneumonia caused by β-lactamase-negative
H. influenzae
d) Shigellosis
III. Extended-spectrum penicillins
2) Amoxicillin
a) Acute nonserious bacterial infections like otitis
media and sinusitis.
b) Multidrug regimens for the eradication of H.
pylori in duodenal and gastric ulcers
c) Prophylactically by dentists for patients with
abnormal heart valves who are to undergo
extensive oral surgery
IV. Antipseudomonal penicillins
• Agents: ticarcillin, and piperacillin
• They are effective against many gram-negative
rods, including Pseudomonas, enterobacter and
in SOME CASES klebsiella species
• Susceptible to penicillinase
• Syngestic effect when used in combination
with aminoglycosides
Resistance
1) Elaboration of the enzyme ß-lactamase, which
hydrolyzes the ß-lactam ring (loss of bactericidal
activity)
2) Alteration of penicillin-binding proteins (PBPs) either
by mutation of existing PBP genes or, more
importantly, by acquiring new PBP genes (e.g.
staphlococcal resistance to methicillin) or by
acquiring new "pieces" of PBP genes (e.g.
pneumococcal, gonococcal and meningococcal
resistance)
3) Resistance seen in gram-negative bacteria, is due to
alteration of genes that specify outer membrane
proteins (porins) and reduce permeability to
penicillins
Adverse Reactions to Penicillins
• Hypersensitivity reactions:
• Are the most common
• All penicillins are cross-sensitizing and crossreacting
• Include:Macropapular rash, urticarial rash, fever ,
bronchospasm , vasculitis , exfoliative dermatitis,
stevens-Johnson syndrome, anaphylaxis (very
rare-0.05% of recipients)
• GIT disturbances: with oral penicillin caused by direct
GIT irritation or overgrowth of gram positive organism
or yeast
β-lactamase inhibitors
•Agents: Clavulanic acid, sulbactam, &
tazobactam
•They Contain β-lactam ring but do not
have significant antibacterial activity
•They bind to & inactivate β-lactamases,
thereby protecting the antibiotics that are
normally substrates for these enzymes
β-lactamase inhibitors
Penicillin plus β-lactamase Inhibitors:
1)
2)
3)
4)
Amoxicillin-clavulanic acid
Ticarcillin-clavulanic acid
Ampicillin-sulbactam
Piperacillin-tazobactam
Cephalosporins & Cephamycins
• Cephalosporins are similar to penicillins, but more
stable to many bacterial β-lactamases and
therefore have a broader spectrum of activity
• Cephalosporins can be classified into five major
groups or generations, depending mainly on the
spectrum of antimicrobial activity & resistance to
β-lactamases
I. First generation
Agents: Cefadroxil, cefazolin, cephalexin,
cephalothin, cephapirin, & cephradine
Penicillin G substitiutes
Have good activity against gram-positive cocci (with
the exception of enterococci, methicillin-resistant S.
aureus, and S. epidermidis) and relatively modest
activity against gram-negative microorganisms
Most mouth anaerobes are sensitive, but the B.
fragilis group is resistant
•Cefazolin penetrates well into most tissues. It is the drug
of choice for surgical prophylaxis. Cefazolin DOES NOT
penetrate the CENTRAL NERVOUS SYSTEM and
cannot be used to treat meningitis
II. Second Generation
• Cefaclor, cefamandole, cefonicid, cefuroxime,
cefprozil, loracarbef, and ceforanide,
cephamycins cefoxitin, cefmetazole, and
cefotetan
• Have somewhat increased activity against gramnegative microorganisms:
– H influenzea
– Enterobacter areogenes
– Some Niesseria species
• As with 1st generation: none is active against
enterococci or P aeuroginosa
Clinical Uses
1. Used to treat otitis, sinusitis and lower RTI (H
influenza & B catarrhallis)
2. Cefoxitin, cefotetan or cefmetazole: used to treat
mixed anaerobic infections such as peritonitis or
diverticulitis
3. Cefuroxime community acquired pneumonia
The only to cross the BBB,
however less effective 3rd
generation
III. Third Generation
• ceftriaxone, cefotaxime, ceftazidime, ceftizoxime, cefoperazone,
cefixime, cefpodoxime proxetil, cefdinir, cefditoren pivoxil,
ceftibuten, and moxalactam
• Expanded gram negative coverage (except cefoperazone)
• The ability to cross the BBB
• Active against citrobacter, Serratia marscens and providentia (but
not the resistant strains)
• Active against B-lactamase producing strains of haemophilus and
neisseria
• Ceftazidime & cefoperazone: the 2 third generation which are
active against P aeureginosa
Third Generation-kinetics
•They penetrate body fluids and tissues well
•Achieve levels in the CSF (With the exception of
cefoperazone, cefixime, cefpodoxime proxetil)
sufficient to inhibit most pathogens
•Excretion of cefoperazone and ceftriaxone is mainly
through biliary tract
•The rest are excreted by the kidney
Fourth Generation
• Cefepime
• it may be useful in treatment of enterobacter
infections. Otherwise, its clinical role is similar
to that of third-generation cephalosporins.
• Cefepime has good activity against most
penicillin-resistant strains of streptococci
• V. Fifth generation
• Agents: Ceftaroline fosamil, the prodrug of ceftaroline
• Effectively bind to and inhibit penicillin-binding
protein 2a, which mediates methicillin-resistance in
staphylococci
Adverse Effects of cephalosporins
• Allergy: identical to penicillins- cross
allerginicity 5-10%
• Toxicity
• Severe pain (IM)
• Thrombophelebitis (IV)
• Renal toxicity,
• Hypoprothrombinemia
• Disulfiram like reaction
• Superinfection
Monobactams: Aztreonam
• Spectrum of activity is limited to aerobic gramnegative rods, including P. aeruginosa
• Has no activity against gram-positive bacteria or
anaerobes
• It is administered either IV or IM and is excreted in the
urine
• it shows little cross-reactivity with other β-lactam
antibiotics
• ADRs: phlebitis, skin rash, and abnormal liver
function tests
Carbapenems: Imipenem
• It is a carbapenem with low susceptibility to B-lactamses
• Wide spectrum activity against many gram-negative rods,
including P aeruginosa, gram-positive organisms, and
anaerobes
• It is resistant to most β-lactamases. Administered parenterally
• The drug of choice for enterobacter infections
• Rapidly metabolised by tubular dehydropeptidase
IMIPENEM-CILASTATIN
•CILASTATIN is a peptidase inhibitor that
blocks renal degradation of Imipenem
•Cilastatin increases the plasma half-life of
imipenem and inhibits the formation of
potentially nephrotoxic metabolite
•ADE: GI distress, skin rash, CNS toxicity
(confusion, encephalopathy and seizures)
•Partial cross allergenicity with penicillins
Vancomycin
• It is active only against gram-positive
bacteria, particularly staphylococci
• No activity against gram-negative
organisms
• Vancomycin is poorly absorbed from the
intestinal tract and is administered orally
only for the treatment of antibioticassociated enterocolitis caused by C
difficile
VANCOMYCIN
•Mechanism of action: Inhibits bacterial cell wall synthesis
by binding firmly to the D-Ala-D-Ala terminus of nascent
peptidoglycan pentapeptide
•Resistance: modification of the D-Ala-D-Ala binding site
of the peptidoglycan in which D-Ala is replaced by D-lactate
(enerococci & vancomycin resistant S aureus)
•Vancomycin kills staphylococci relatively slowly and only if
cells are actively dividing;
•The combination of vancomycin and gentamicin is
synergistic against Staphylococcus aureus and enterococci
Clinical uses of vancomycin
1.
2.
3.
4.
5.
Main indication is: sepsis or endocarditis caused by MRSA
Methicillin-susceptible staphylococci in patients who are
allergic to penicillins or cephalosporins
Vancomycin in combination with gentamicin is an
alternative regimen for treatment of enterococcal
endocarditis in a patient with serious penicillin allergy
Vancomycin (in combination with cefotaxime, ceftriaxone,
or rifampin) is also recommended for treatment of
meningitis suspected or known to be caused by a highly
penicillin-resistant strain of pneumococcus
Oral vancomycin is used to treat antibiotic-associated
enterocolitis caused by Clostridium difficile
Adverse
reactions
1) Phlebitis at site of injection
2) Ototoxicity and Nephrotoxicity are rare with
current preparations.
3) AVOID coadministration with
aminoglycosides
4) Red man or red neck syndrome: infusion
related flushing due to histamine release
(slow infusion over 2hrs, increase dilution
volume, or pretreat with antihistamine)
Protein Synthesis Inhibitors
• Target the bacterial ribosome, which has
components that differ structurally from those of
mammalian cytoplasmic ribosomes
• The bacterial ribosome consists of a 50S subunit
and a 30S subunit, whereas in the mammalian
ribosome the subunits are 60S and 40S
1. Chloramphenicol 2. Tetracyclines
3. Macrolides 4. Clindamycin
5. Aminoglycosides 6. Linezolide
7. Streptogramines
Aminoglycosides
• Agents: streptomycin, neomycin, kanamycin, amikacin,
gentamicin, tobramycin, sisomicin, netilmicin
• Aminoglycosides have been used in paediatric patients for
more than 60 years
• They
have concentration-dependent killing & a
significant postantibiotic effect
• They are not available for oral administration, so they
are mainly used in parenteral form
• Predominantly used to treat gram-negative treat bacteria
infections including Pseudomonas spp,
• They are useful in the treatment of UTIs, intra-abdominal
infections, neonatal sepsis, complicated infections in cystic
fibrosis, and as empiric therapy for febrile neutropenic
patients
Aminoglycosides
• Aminoglycosides have concentration-dependent
killing & a significant postantibiotic effect
• Optimal dosing strategies of aminoglycosides include
high doses administered once daily (extended-interval
dosing)
• The three most commonly used agents are:
gentamicin, tobramycin, and amikacin
• Aminoglycosides frequently exhibit synergism with
beta lactams
Adverse effects
1.
2.
Ototoxicity
Nephrotoxicity
3. Neuromuscular paralysis:
• Most often occurs after direct intraperitoneal or
intrapleural application of large doses of
aminoglycosides
• Caused by a decrease in both the release of
acetylcholine from prejunctional nerve endings and the
sensitivity of the postsynaptic site
• Reversible by calcium gluconate (promptly) or
neostigmine
Tetracylcins
• Agents: Tetracyclin, minocycline, doxycycline,
demeclocycline, & oxytetracycline
• Bacteriostatic broad spectrum antibiotics: active
against a wide range of aerobic and anaerobic
gram-positive and gram-negative bacteria, as
well as against some protozoa, eg, amebas
• Bind reversibly to 30S of bacterial ribosome,
blocking the binding of aminoacyl-tRNA to the
acceptor site on the mRNA-ribosome complex
Tetracylcins
• The antibacterial activities of most tetracyclines
are similar except that tetracycline-resistant
strains may be susceptible to doxycycline,
minocycline, and tigecycline
• Absorption is impaired by divalent cations (Ca2+,
Mg2+, Fe2+) or Al3+; by dairy products and
antacids, and by alkaline pH
• Tetracyclines cross the placenta to reach the fetus
and are also excreted in milk
Typical therapeutic applications of tetracyclines
Adverse effects
1. GIT: N,V, and diarrhea (most common) due to
direct irritation of the intestine. Modify normal
flora
2. Bony Structures and Teeth:deposition in the bone
and primary dentition occurs during calcification
in growing children. This causes discoloration
and hypoplasia of the teeth and a temporary
stunting of growth
Therefore, tetracyclines
are generally avoided
in pregnancy & for long periods
to children under 8 years of age
Adverse effects
3. Fatal hepatotoxicity: especially during pregnancy
4. Phototoxicity: such as severe sunburn, occurs when a
patient receiving a tetracycline ,especially
demeclocycline, is exposed to sun or ultraviolet rays
5. Local Tissue Toxicity (IV & IM injections)
6. Vestibular Reactions (dizziness, vertigo, N, & V)
particularly with minocycline
7. Superinfections: Overgrowths of Candida (for
example, in the vagina) or of resistant staphylococci
(in the intestine)
Macrolides
• Agents: erythromycin, clarithromycin, azithromycin,
telithromycin (Ketolide)
• The macrolides, in general, are bacteriostatic
• Erythromycin may be bactericidal, particularly at
higher concentrations, for susceptible organisms
• Inhibition of protein synthesis occurs via binding to the
50S ribosomal RNA
• Erythromycin base is destroyed by gastric acid. Thus,
either enteric-coated tablets or esterified forms of the
antibiotic are administered
Typical therapeutic applications of macrolides
Macrolides-ADRs
• Epigastric distress: Anorexia, nausea, vomiting,
and diarrhea. Can lead to poor patient compliance
for erythromycin
• Cholestatic jaundice: especially with the estolate
form of erythromycin as the result of a
hypersensitivity reaction
• Prolongate the QTc interval in some patients
(Telithromycin): avoided in patients with
congenital prolongation of the QTc interval and in
those patients with proarrhythmic conditions
Lincosamides
• Agents: Clindamycin
• Similar mechanism of action to macrolides
• Clindamycin is employed primarily in the
treatment of infections caused by ANAEROBIC
bacteria, such as Bacteroides fragilis, which often
causes abdominal infections associated with
trauma
• It is also significantly active
nonenterococcal, gram-positive cocci
against
Clindamycin
• ADRs:
1) Skin rash
2) Pseudomembranous colitis caused by overgrowth of
C. Difficile characterized as potentially fatal diarrhea
coupled with abdominal cramping and excretion of
blood or mucus
• Oral administration of either vancomycin or
metronidazole is usually effective in controlling this
serious condition
3) Impaired liver function
Chloramphenicol
• Chloramphenicol is a broad-spectrum antibiotic that is
active against both aerobic and anaerobic grampositive and gram-negative organisms
• It binds reversibly to the 50S of bacterial ribosomes
• It is active also against rickettsiae
• The drug is either bactericidal or (more commonly)
bacteriostatic, depending on the organism
Clinical Uses
• Topically in the treatment of eye infections b/c of its broad
spectrum and its penetration of ocular tissues and the
aqueous humor
Clinical Uses
1) Alternative to a β-lactam antibiotic for treatment of
meningococcal meningitis occurring in patients who
have major hypersensitivity reactions to penicillin or
bacterial meningitis caused by penicillin-resistant
strains of pneumococci
2) Treatment of serious rickettsial infections such as
typhus
Adverse Effects
1) GIT disturbances: NVD
2) Oral or vaginal candidiasis: overgrowth of
Candida albicans
Chloramphenicol Adverse Effects
3. Bone Marrow Disturbances: dose-related reversible
suppression of RBCs production & aplastic anemia
especially in patients with low levels of glucose 6phosphate dehydrogenase
4. Gray baby syndrom: vomiting, flaccidity,
hypothermia, gray color, shock, and collapse
• Neonates have a decreased ability to excrete the drug,
which accumulates to levels that interfere with the
function of mitochondrial ribosomes
Streptogramines
• A combination of 2 antibiotics: quinupristin &
dalfopristin in a 3:7 wt/wt ratio
• Each component bind to a separate site on the 50S
bacterial ribsome, forming a stable ternary compound
(synergistic effect)
• Bactericidal primarily against G+ve cocci including
those resistant to other antibiotics (MRSA and
VERSA)
• Bacteriostatic against Enterococcus faecium
• Approved for treatment of infections caused by
staphylococci or by vancomycin-resistant strains of
E faecium
Streptogramines- ADRs
1) Pain at infusion site
2) Arthralgia & myalgia (high doses)
3) Hyperbilirubinema (25% of patients)
Antimetabolites
Sulfonamides and trimethoprim
Indirect nucleic acid synthesis inhibitors
Sulfonamides:
• Bacteriostatic rather than bactericidal
• Strctural/ synthetic analogus of p-aminobenzoic acid:
they are competitive inhibitors of dihydropteroate
synthase
• The selective toxicity of sulfonamides results from the
inability of mammalian cells to synthesize folic acid;
they must use preformed folic acid that is present in the
diet
Sulfonamides
•The sulfonamides may be classified as:
1. Topical (not commonly b/c of the risk of
sensitization)
2. Oral nonabsorbable (Sulfasalazine)
3. Oral absorbable
– Short-acting (eg, sulfisoxazole)
– Intermediate-acting (eg, sulfamethoxazole)
– Long-acting (eg, sulfadoxine)
Sulfonamides – Clinical uses
1) Oral abosrbable:
•
Toxoplasmosis: Oral sulfadiazine plus pyrimethamine (a
DHF reductase inhibitor) plus folinic acid
•
Simple urinary
sulfamethoxazole
tract
infections:
Sulfisoxazole
and
2) Topical agents:
•
•
Bacterial conjunctivitis: sodium sulfacetamide ophthalmic
solution or ointment
Prevention of infection of burn wounds: silver sulfadiazine
3) Oral nonabsorbalbe: ulcerative colitis, rheumatoid arthritis:
Oral (sulfasalazine; sulfapyridine and 5-aminosalicylic acid
(5-ASA))
Sulfonamides – Adverse effects
1)
Hypersensitivity: Allergic reactions, including skin rashes and fever
•
Cross-allergenicity between the individual sulfonamides should be assumed and
may also occur with chemically related drugs (eg, oral hypoglycemics, thiazides)
2)
GIT: NVD
3)
Hematotoxicity: granulocytopenia, aplastic anemia, & thrombocytopenia
•
Acute hemolysis may occur in persons with glucose-6-phosphate dehydrogenase
deficiency
4.
Crystalluria:
– Sulfonamides may precipitate in the urine at acidic pH
– Adequate hydration and alkalinization of urine prevent the
problem
5. Kernicterus: Sulfonamides can displace bilirubin from plasma
proteins & bilirubin is then free to pass into the CNS
– Should be avoided in newborns and infants less than 2 months of
age as well as in pregnant women at term
Trimethoprim – Mechanism of action
•An analog of dihydrofolic acid
Trimethoprim is a selective inhibitor of bacterial dihydrofolate
reductase that prevents formation of the active tetrahydro- form of
folic acid
Bacterial dihydrofolate reductase is four to five orders of magnitude
more sensitive to inhibition by trimethoprim than the mammalian
enzyme
Alone can be given in acute urinary tract infections
•Adverse effects may cause the predictable adverse effects of an
antifolate drug, including
1) Megaloblastic anemia
2)
Leukopenia
3)
Granulocytopenia
•These effects are usually ameliorated by supplementary folinic acid
Trimtethoprim plus sulfamethoxazole (TMPSMZ)
• The combination of trimethoprim with sulfamethoxazole is called
cotrimoxazole
• When the two drugs are used in combination, antimicrobial synergy
results from the sequential blockade of folate synthesis
• The drug combination is bactericidal against susceptible organisms
• Adverse effects
•
The combination of trimethoprim-sulfamethoxazole may cause any of
the adverse effects associated with the sulfonamides
•
AIDS patients given TMP-SMZ have a high incidence of adverse
effects, including fever, rashes, leukopenia, and diarrhea.
Typical therapeutic applications of co-trimoxazole (sulfamethoxazole
plus trimethoprim).
Quinolone Antimetabolite
Fluoroquinolones
Ciprofloxacin
Norflxacin
Moxifloxacin
Levofloxacin
Direct nucleic acid synthesis inhibitors
Fluoroquinolones
• Broad-spectrum antibiotic effective against a variety
of gram-positive and gram-negative bacteria
• They block bacterial DNA synthesis by inhibiting
bacterial:
1) Topoisomerase II (DNA gyrase): prevents the relaxation of
positively supercoiled DNA that is required for normal
transcription and replication
2) Topoisomerase IV: interferes with separation of replicated
chromosomal DNA into the respective daughter cells during
cell division
• Originally developed because of their excellent activity
against gram-negative aerobic bacteria; they had
limited activity against gram-positive organisms
Fluoroquinolones
• Several newer agents have improved activity
against gram-positive cocci
• The relative activity against gram-negative vs.
gram-positive species is useful for classification of
these agents.
• Clinical uses
• UTI even when caused by multidrug-resistant
bacteria, eg, pseudomonas
• Bacterial diarrhea caused by shigella,
salmonella,
toxigenic
E
coli,
and
campylobacter
Clinical uses
• Infections of soft tissues, bones, and joints and in intraabdominal and respiratory tract infections, including
those caused by multidrug-resistant organisms such as
pseudomonas and enterobacter (except norfloxacin)
• Quinolones – Clinical uses
•
Ciprofloxacin is a DOC for prophylaxis and treatment of
anthrax
•
Ciprofloxacin and levofloxacin
chlamydial urethritis or cervicitis
•
Ciprofloxacin, levofloxacin, or moxifloxacin is occasionally used
for treatment of tuberculosis and atypical mycobacterial
infections
•
Respiratory fluoroquinolones (e.g. levofloxacin, gatifloxacin,
gemifloxacin, & moxifloxacin): upper and lower RTI
are
effective
in
treating
Adverse effects
1) GIT: NVD (most common)
2) CNS: headache and dizziness or light-headedness
3) Phototxicity
4) Connective tissue problems: may damage growing
cartilage and cause an arthropathy. Thus, these drugs are not
routinely recommended for patients under 18 years of age
5) QT interval prolongation: with gatifloxacin, levofloxacin,
gemifloxacin, and moxifloxacin