Transcript Chapter 17

Chapter 17
Anti-Infective Drugs
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Introduction
• Treatment of infection
– Complicated by the great variety of
medications available and their differing
modes of action
– First step: identify the causative organism and
specific medication to which it is sensitive
• Culture and sensitivity (C&S) tests
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Resistance
• Organisms may build up resistance to
drugs and are therefore, no longer
effective because of:
– Frequent use
– Incomplete treatment
• Anti-infective resistance is caused by
many factors
– Complex strategies needed to combat the
problem
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Resistance (cont’d.)
• Selection of anti-infective drugs
– Infection site
– Status of hepatic and/or renal function
– Patient age
– Pregnancy or lactation
– Likelihood of organisms developing resistance
– Known allergy to the anti-infective drug
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Adverse Reactions
• Categories
– Allergic hypersensitivity
• Over-response of the body to a specific substance
– Direct toxicity
• Results in tissue damage
– Indirect toxicity or superinfection
• Manifested as a new infection due to absence of
normal flora in the intestines or mucous
membranes
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Vaccines/Immunizations
• Centers for Disease Control and
Prevention (CDC)
– Currently recommends routine vaccination
• Prevent 17 vaccine-preventable diseases that
occur in infants, children, adolescents, or adults
• Information regarding vaccines and immunizations
changes from time to time and requirements may
vary by state, territory, or country
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Aminoglycosides
• Treats many infections caused by:
– Gram-negative bacteria (e.g., Escherichia coli
and Pseudomonas)
– Gram-positive bacteria (e.g., Staphylococcus
aureus)
• Effective in short-term treatment of many
serious infections
– Septicemia (e.g., bacteria in bloodstream
causing low blood pressure) when less toxic
drugs are ineffective or contraindicated
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Cephalosporins
• Semisynthetic beta-lactam antibiotic
derivatives produced by a fungus
– Related to penicillins
• Some patients allergic to penicillin are also allergic
to cephalosporins
• Classified as first, second, third, or fourth,
or fifth generation
– According to organisms susceptible to their
activity
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Macrolides
• Treats many infections of the respiratory
tract, skin conditions, or for some sexually
transmitted infections
– Considered among the least toxic antibiotics
• Preferred for treating susceptible organisms under
conditions in which more toxic antibiotics might be
dangerous
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Penicillins
• Beta-lactam antibiotics produced from
certain species of a fungus
– Treats many streptococcal and some
staphylococcal and meningococcal infections
– Drug of choice for treatment of syphilis
– Used prophylactically to prevent recurrences
of rheumatic fever
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Carbapenems
• Belong to the beta-lactam class of
antibiotics
– Have a very broad spectrum of activity
against gram-negative and gram-positive
organisms
– Primary treatments include pneumonia, febrile
neutropenia, intra-abdominal infections,
diabetic foot infections, and significant
polymicrobial infections
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Quinolones
• For adult treatment of some infections of
the urinary tract, sinuses, lower respiratory
tract, GI tract, skin, bones, and joints, and
in treating gonorrhea
– Some organisms are showing increased
resistance
– Reserve for infections that require therapy
with a fluoroquinolone
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Tetracyclines
• Broad-spectrum antibiotics
– Treats infections caused by rickettsia,
chlamydia, or some uncommon bacteria
– Some organisms are showing increasing
resistance
– Use only when other antibiotics are ineffective
or contraindicated
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Antifungals
• Treat specific susceptible fungal disease
– Medications are quite different in action and
purpose
• Amphotericin B
– Administered IV for the treatment of severe
systemic and potentially fatal infections
caused by susceptible fungi, including
Candida
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Antifungals (cont’d.)
• Fluconazole
– Works against many fungal pathogens,
including most Candida, without the serious
toxicity of amphotericin B
• Micafungin (Mycamine)
– Given IV
– Provides new treatment options against
Candida and Aspergillus species
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Antifungals (cont’d.)
• Nystatin
– Structurally related to Amphotericin B
– Orally treats oral cavity candidiasis
– Also used as a fungicide in the topical
treatment of skin and mucous membranes
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Antituberculosis Agents
• Tuberculosis (TB)
– Caused by a bacterium called Mycobacterium
tuberculosis, which primarily attacks the lungs
• Antituberculosis agents are administered
for two purposes
– To treat latent or asymptomatic infection (no
evidence of clinical disease)
– For treatment of active clinical tuberculosis
and to prevent relapse
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Miscellaneous Anti-Infectives
• Clindamycin
– Treats serious respiratory tract infections,
septicemia, osteomyelitis, serious infections
of the female pelvis caused by susceptible
bacteria, and for Pneumocystis jirovecii
pneumonia associated with AIDS
– Prophylactic use in dental procedures for
penicillin-allergic patients
– May be a viable therapeutic option for
community-acquired MRSA
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Miscellaneous Anti-Infectives
(cont’d.)
• Metronidazole (Flagyl)
– Synthetic antibacterial and antiprotozoal
agent
– Effective against protozoa
– One of the most effective drugs against
anaerobic bacterial infections
– Also useful in treating Crohn’s disease,
antibiotic-associated diarrhea, rosacea, and
H. pylori infection
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Miscellaneous Anti-Infectives
(cont’d.)
• Vancomycin
– Structurally unrelated to other available
antibiotics
– IV vancomycin is used in the treatment of
potentially life-threatening infections caused
by susceptible organisms
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Agents for VRE
• Linezolid (Zyvox)
– Indicated for gram-positive infections
– Approved for the treatment of bacterial
pneumonia skin, skin structure infections, and
MRSA and VRE infections
– Effective in treating diabetic foot infections
– Administered by IV infusion or orally
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Sulfonamides
• Among the oldest anti-infectives
– Increasing resistance of many bacteria has
decreased the clinical usefulness of these
agents
• Used most effectively in combinations with
other drugs
– Example: sulfamethoxazole and trimethoprim
– Resistance develops more slowly
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Urinary Anti-Infectives
• Urinary tract infection (UTI)
– Symptomatic inflammatory response from the
presence of microorganisms in the urinary
tract
– One of the most common bacterial infections
for which patients seek treatment
– First-line urinary anti-infectives for empiric
treatment of uncomplicated lower UTI are
sulfamethoxazole-trimethoprim and
nitrofurantoin
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Antivirals
• Acyclovir
– Primarily treats herpes simplex, herpes zoster
(shingles), and varicella zoster (chickenpox)
infections
• Neuraminidase inhibitors
– Indicated for the treatment of uncomplicated
acute illness due to influenza types A and B
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Antivirals (cont’d.)
• Ribavirin
– Treats infants and young children with
respiratory syncytial virus (RSV) infections via
nasal and oral inhalation
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Treatment of HIV/AIDS Infections
• Highly specialized field
– Those actively practicing in that field must be
updated frequently on the many new
medications and frequently changing
protocols
• Treatment of HIV infection
– Consists of using highly active antiretroviral
therapy (HAART) combinations of three or
more antiretroviral (ARV) agents
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Treatment of HIV/AIDS Infections
(cont’d.)
• Antiretroviral protease inhibitors (PIs)
– Block the activity of the HIV enzyme essential
for viral replication late in the virus life cycle
• Nucleoside reverse transcriptase inhibitors
(NRTIs)
– Inhibit an enzyme responsible for viral
replication early in the virus life cycle
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Treatment of HIV/AIDS Infections
(cont’d.)
• Non-nucleoside reverse transcriptase
inhibitors (NNRTIs)
– Inhibit an enzyme responsible for viral
replication early in the viral life cycle
• Fusion inhibitors (FIs)
– Block entry of HIV into cells, which may keep
the virus from reproducing
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Treatment of HIV/AIDS Infections
(cont’d.)
• CCR5 antagonists
– Block a co-receptor required for HIV entry into
human cells
• Integrase inhibitor
– Raltegravir (Isentress): first ARV designed to
slow the advancement of HIV infection by
blocking the enzyme needed for viral
replication
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HIV Information and Resources
• Sources of current recommendations for
clinical use of antiretrovirals (ARVs)
– Department of Health and Human Services
– Florida/Caribbean Aids Education and
Training Center
– AETC National Resource Center Drug
Interactions
– Johns Hopkins HIV Guide
– National HIV Telephone Consultation Service
– University of California, San Francisco
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