DRUG SUMMARY TABLE: CHAPTER 34 Pharmacology of Bacterial Infections: DNA Replication, Transcription, and Translation
DRUG CLINICAL APPLICATIONS
INHIBITORS OF TOPOISOMERASES: QUINOLONES
Mechanism—Inhibit bacterial type II topoisomerases. At therapeutic concentrations, quinolones have a bactericidal effect by causing dissociation of the
topoisomerase from cleaved DNA, leading to double-stranded DNA breaks and cell death.
Ciprofloxacin Respiratory tract infection
Gemifloxacin (ciprofloxacin,
Levofloxacin gemifloxacin, levofloxacin,
Moxifloxacin moxifloxacin, and
Norfloxacin ofloxacin only)
Ofloxacin Gastrointestinal tract
infection (ciprofloxacin,
levofloxacin, and
moxifloxacin only)
Infection of
skin/subcutaneous tissue
(ciprofloxacin,
levofloxacin, moxifloxacin,
and ofloxacin only)
Urinary tract infection
(ciprofloxacin,
levofloxacin, norfloxacin,
and ofloxacin only)
Eye infection
(levofloxacin,
moxifloxacin, norfloxacin,
and ofloxacin only)
Bone infection
(ciprofloxacin only)
Ear infection (ofloxacin
only)
Nalidixic Acid Urinary tract infection
SERIOUS & COMMON ADVERSE EFFECTS CONTRAINDICATIONS THERAPEUTIC CONSIDERATIONS
Prolonged QT interval, myasthenia gravis Shared contraindication: Bacteria evolve resistance through
exacerbation, cartilage damage, tendon  Hypersensitivity to chromosomal mutations in the
rupture, peripheral neuropathy (shared quinolones genes that encode type II
adverse effects); severe hypersensitivity Ciprofloxacin only: topoisomerases or through
reaction, bone marrow depression,  Concomitant alterations in the expression of
hepatotoxicity, nephrotoxicity, retinal tizanidine membrane porins and efflux
detachment (ciprofloxacin, levofloxacin, administration pumps that determine drug levels
moxifloxacin, norfloxacin, and ofloxacin inside the bacteria.
only); Clostridium difficile diarrhea Avoid co-administration with
(ciprofloxacin, norfloxacin, and ofloxacin drugs that prolong QT interval due
only); seizure (ciprofloxacin and ofloxacin to increased risk of cardiotoxicity.
only); increased intracranial pressure, Limited use in children under 18
pancreatitis, psychotic disorder years of age due to arthropathy in
(ciprofloxacin only); extrapyramidal juvenile animals and increased
disease (ofloxacin only) adverse events involving joints
Rash, gastrointestinal disturbance and surrounding tissues (e.g.,
(shared adverse effects); burning tendons) in pediatric patients.
sensation in eye (ofloxacin only)
Prolonged QT interval, porphyria, Hypersensitivity to One of the earliest quinolones to
metabolic acidosis, paralytic ileus, nalidixic acid enter clinical use.
 hemolytic anemia, thrombocytopenia, Concomitant use with Nalidixic acid is no longer
hypersensitivity reaction, cartilage chemotherapeutic marketed in the United States.
damage, tendon rupture, increased alkylating agents
intracranial pressure, peripheral History of seizure
neuropathy, seizure, psychotic disorder disorder
Infants under 3 months
of age
Mothers who are
breastfeeding
Porphyria
INHIBITORS OF TRANSCRIPTION: FIDAXOMICIN AND RIFAMYCIN DERIVATIVES
Mechanism—Form a stable complex with bacterial DNA-dependent RNA polymerase, thereby inhibiting RNA synthesis
Fidaxomicin Treatment of Clostridium Bowel obstruction, gastrointestinal Hypersensitivity to Efficacy is similar to standard
difficile-associated hemorrhage, neutropenia, anemia fidaxomicin therapy for initial cure, with lower
diarrhea Gastrointestinal upset rate of relapse with fidaxomicin.
Rifabutin Mycobacterial infections, Agranulocytosis, hypersensitivity reaction Shared Rifampin is not used as a single
Rifampin including tuberculosis (shared adverse effects); hepatotoxicity, contraindications: agent because of rapid
(shared indication) nephrotoxicity (rifampin only)  Hypersensitivity to development of resistance.
Prophylaxis of Rash, gastrointestinal upset, elevated drug Rifampin may reduce cyclosporine
meningococcal disease liver function tests, discoloration of  Concomitant use concentration and efficacy.
(rifampin only) saliva, tears, sweat, and urine (rifabutin with rilpivirine Avoid concurrent administration
only) Rifampin only: of clarithromycin with rifabutin
 Concomitant use because clarithromycin increases
with atazanavir, plasma concentration of rifabutin
darunavir, and rifabutin reduces plasma
fosamprenavir, concentration of clarithromycin.
saquinavir, or
tipranavir
ANTIMICROBIAL DRUGS TARGETING THE 30S RIBOSOMAL SUBUNIT
Mechanism—Bind to 16S rRNA of the 30S ribosomal subunit and elicit concentration-dependent effects on protein synthesis. Aminoglycosides are bactericidal,
evidently due to induction of mRNA misreading; misread mRNA causes synthesis of aberrant proteins that may activate oxidative stress pathways and/or insert
into the cell membrane, forming pores that eventually lead to cell death. Other drugs are bacteriostatic.
Aminoglycosides: Serious Gram-negative Respiratory paralysis (shared adverse Shared contraindication: Act synergistically with β-lactam
 Amikacin infections effect); nephrotoxicity (shared adverse  Hypersensitivity to antibiotics.
 Gentamicin effect excepting tobramycin); ototoxicity aminoglycosides Resistance can occur by three
 Kanamycin (amikacin, gentamicin, kanamycin, Neomycin and mechanisms:
 Neomycin neomycin, netilmicin, and tobramycin paromomycin only:  1.Plasmid-encoded
 Netilmicin only); neuromuscular blockade (amikacin,  Gastrointestinal production of a transferase
 Paromomycin gentamicin, kanamycin, neomycin, and disease enzyme or enzymes that
 Streptomycin netilmicin only); facial paresthesia inactivate aminoglycosides
 Tobramycin (streptomycin only)  2.Impaired drug entry,
Gastrointestinal upset, rash possibly by alteration or
elimination of porins or
other proteins involved in
drug transport
 3.Mutation of the drug
target on the 30S ribosomal
subunit
Spectinomycin Gonorrhea (alternative Injection site pain, nausea, dizziness, Hypersensitivity to Permits formation of the 70S
therapy) insomnia spectinomycin ribosome but inhibits
translocation.
Tetracyclines: Used to treat a variety of Nephrotoxicity (demeclocycline and Shared contraindication: Tetracyclines antagonize the
 Demeclocycline infections, notably those tetracycline only); hypersensitivity  Hypersensitivity to bactericidal effects of penicillins,
 Doxycycline due to Propionibacterium reaction, Clostridium difficile diarrhea, drug and this antagonism likely occurs
 Minocycline acnes, Vibrio cholerae, hepatotoxicity, pseudotumor cerebri Tetracycline only: with any combination of a
 Tetracycline Borrelia burgdorferi, (doxycycline, minocycline, and  Last half of bacteriostatic inhibitor of protein
Helicobacter pylori, tetracycline only) pregnancy, synthesis and a β-lactam drug or
Mycoplasma pneumoniae, Photosensitivity, gastrointestinal upset, infancy, childhood an aminoglycoside.
Chlamydia species, and tooth discoloration, headache (shared up to 8 years of Tetracyclines are actively
rickettsial species (shared adverse effects) age transported into bacterial cells.
indications) Resistance occurs by plasmid-
Malaria prophylaxis encoded efflux pumps, production
(doxycycline only) of proteins that interfere with
binding of tetracyclines to the
 ribosome, or enzymatic
inactivation of tetracyclines.
Tetracycline should be taken on an
empty stomach because calcium
products interfere with
absorption.
Avoid co-administration with
acitretin due to increased risk of
elevated intracranial pressure.
Glycylcyclines: Complicated skin or Septic shock, Clostridium difficile Hypersensitivity to Structure is similar to
 Tigecycline subcutaneous infection diarrhea, pancreatitis, hepatotoxicity, tigecycline tetracyclines.
Complicated abdominal hypersensitivity reaction, pseudotumor
infection cerebri
Community-acquired Gastrointestinal upset
bacterial pneumonia
ANTIMICROBIAL DRUGS TARGETING THE 50S RIBOSOMAL SUBUNIT
Mechanism—Bind to a small region of 23S rRNA of the 50S ribosomal subunit near the peptidyl transferase active center. All drugs are bacteriostatic except for
streptogramins, which can be bactericidal.
Macrolides and Ketolides: Erythromycin is used to Prolonged QT interval, hepatotoxicity, Shared Resistance can be conferred by
 Azithromycin treat a variety of hypersensitivity reaction (shared adverse contraindications: chromosomal mutations leading
 Clarithromycin infections, notably those effects); exacerbation of myasthenia  Hypersensitivity to to alteration of the 50S ribosomal
 Erythromycin due to Propionibacterium gravis (azithromycin and telithromycin drug binding site, production of
 Telithromycin acnes, Legionella only); Eaton-Lambert syndrome, corneal  Hepatic methylases that alter the 50S
pneumophila, erosion (azithromycin only); Clostridium dysfunction binding site, or production of
Mycoplasma pneumoniae, difficile diarrhea (clarithromycin and Clarithromycin and esterases that degrade
and Chlamydia species erythromycin only); pancreatitis, seizure, telithromycin only: macrolides.
Clarithromycin has ototoxicity, interstitial nephritis  QT prolongation Macrolides and ketolides inhibit
increased activity against (erythromycin only); respiratory failure or ventricular hepatic metabolism of
H. influenzae (telithromycin only) arrhythmias cyclosporine, carbamazepine,
Azithromycin has Gastrointestinal disturbance  Concomitant use warfarin, and theophylline and can
increased activity against with pimozide lead to toxic levels of these drugs.
H. influenzae and Clarithromycin only: Macrolides eliminate certain
Moraxella catarrhalis species of intestinal flora that

Chloramphenicol
Lincosamides:
 Clindamycin
Streptogramins:
 Dalfopristin/Quinupristin Enterococcus faecium
Oxazolidinones:
 Linezolid
 Tedizolid phosphate
 Concomitant use inactivate digoxin, thereby leading
with HMG-CoA to greater oral absorption of
reductase digoxin in some patients.
inhibitors
metabolized by
CYP3A4
Telithromycin only:
 Myasthenia gravis
Broad-spectrum antibiotic Aplastic or hypoplastic anemia, leukemia, Hypersensitivity to Most adverse effects are due to
active against bacteria thrombocytopenia, hepatotoxicity, chloramphenicol inhibition of mitochondrial
(especially anaerobes) and hypersensitivity reaction, optic atrophy, function.
rickettsiae paroxysmal nocturnal hemoglobinuria, Inhibits hepatic metabolism of
gray baby syndrome warfarin, phenytoin, tolbutamide,
and chlorpropamide and thereby
potentiates their effects.
Bacterial infections due to Erythema multiforme, Clostridium difficile Hypersensitivity to Clindamycin is associated with
anaerobic organisms diarrhea, agranulocytosis, increased liver clindamycin overgrowth of C. difficile, which
function tests, jaundice can result in pseudomembranous
Gastrointestinal upset, rash colitis.
Vancomycin-resistant Injection site inflammation, Hypersensitivity to Should not be co-administered
gastrointestinal disturbance, dalfopristin/quinupristin with SSRIs due to risk of serotonin
(VREF) hyperbilirubinemia, arthralgia, myalgia, syndrome.
Skin infections caused by headache Co-administration with pimozide
Staphylococcus aureus or should be avoided due to
Streptococcus pyogenes increased risk of cardiotoxicity (QT
prolongation, torsades de pointes,
cardiac arrest).
Linezolid only: Clostridium difficile diarrhea, peripheral Shared contraindication: Available in both oral and IV
 Gram-positive neuropathy, disorder of optic nerve  Hypersensitivity to formulations. Tedizolid phosphate
bacterial infections, (shared adverse effects); lactic acidosis, drug approved in 2014.
especially myelosuppression, hepatotoxicity, Linezolid only:
vancomycin-
 resistant serotonin syndrome (linezolid only);  Concomitant use
enterococcus, neutropenia (tedizolid phosphate only) of monoamine
methicillin-resistant Gastrointestinal upset, headache oxidase inhibitors
S. aureus (MRSA), S. (MAOIs)
agalactiae, S.
pneumoniae
(including drug-
resistant strains),
and S. pyogenes
 Nosocomial
pneumonia
 Complicated
diabetic foot
infections
Tedizolid phosphate only:
 Acute bacterial skin
and subcutaneous
tissue infections
caused by Gram-
positive cocci
Pleuromutilins: Impetigo due to MSSA or Hypersensitivity reaction No specific Topical application for bacterial
 Retapamulin Streptococcus pyogenes Application site irritation contraindications skin infections.