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Major Concepts of
Antimicrobials
Special Concepts r/t Anitmicrobials
• Selective toxicity
– Ability to target without harming host
• Susceptibility
• Prophylaxis
– Neutropenia, Surgery, Endocarditis
• Combination Therapy
• Misuse – non-specific fevers, viruses
Resistance
Fig 82-1
Aminoglycosides: Bactericidal
Inhibitors of Protein Synthesis
Chapter 86
Aminoglycosides: Background
• Resistance is beginning to limit use
– Gentamicin – cheaper but commonly used
– 20 diff aminoglycoside-inactivating enzymes (like the
beta-lactamases for PCN)
– Reserve amikacin (in this class this is big gun, save it)
• Bactericidal
– concentration dependent (the more you get, the more
it kills)
– Post-antibiotic effect – several hours (it sticks around
a lot longer than some other drugs)
– NOT effective against anaerobes
Gentamicin (Garamycin)
(Prototype)
• MOA / Use: narrow spectrum for gram- bacilli –
esp. pseud. aerugenosa, E. coli, Klebs., Serratia
• ADME:
–
–
–
–
–
–
–
Poor CSF
Not absorbed orally (so?) (typically IV)
Toxicity w/ wound irrigation
Needs Peak and Trough
Binds tightly to renal tissue
Excretion primarily renal
Dosage varies widely (0.5 mg/kg to 25 mg/kg)
•
Adverse Effects
– Ototoxic (if it stays above the baseline for therapeutic levels too long…
want the level to drop low enough so the body can wash it out)
• r/t excess trough levels – sensory hairs
• HA (headache), N, vertigo then high-pitched tinnitis (Action?) If you
noticed tinnitus, first action would be to stop the dose and call the
dr!
– Nephrotoxic
• Total cumulative dose
• ATN (acute tubular necrosis, tube in the nephron gets necrotic and
leads to renal failure.(proteinuria (protein in the blood), casts
(slough big particles), BUN (Blood Urea Nitrogen), Creatinine
• Elderly and young and sick
– Neuromuscular blockade
– Hypersensitivity & blood dyscrasias (rare)
• DD
– PCNs, Cephs, Vanco used in combo
– PCNs inactivate – schedule issue?
– Ethacrynic Acid – will potentiate (increase)
ototoxicity
– Other nephrotoxics
– Skeletal Muscle relaxants (r/t the
neuromuscular blockade which makes them
weak)
Aminoglycosides: Special
Concerns
• Neomycin most nephrotoxic (Not ever IM or IV,
might see it preoperativly to sterilize the gut) Will
also see it topically.
• Scheduling once daily – Safer? (yes, lets trough
get low to wash out of tissue)
– Post-antibiotic effect
– Washout – esp. in vestibule and kidneys
– Typically only measure trough – up to 1hr prior to next
dose – level should be ?
Antifungal Agents
Chapter 91
Antifungal Agents
Systemic mycotic infections
• Opportunistic (r/t infections that set up house in
debilitated pts): candidiasis, aspergillosis,
cryptococcosis, mucormycosis
• Nonopportunistic (ones you get because you were
exposed to it): sporotrichosis, blastomycosis,
histoplasmosis, coccidioidomycosis
Superficial mycotic infections
• Candidiasis
• Dermatophytes
Antifungal Agents
Systemic mycotic (fungal) infections
• Opportunistic – host is sick, debilitated,
immunocompromised pt
– candidiasis, aspergillosis, cryptococcosis,
• Non-opportunistic
– blastomycosis, histoplasmosis,
coccidioidomycosis
Superficial mycotic infections
– Candidiasis
– Dermatophytes (little bugs with sharp teeth on that commercial…)
Antifungals: Major Classes
•
•
•
•
Polyenes
Azoles
Pyrimidine analogs
Echinocandins
Amphotericin B [Fungizone]
MOA / TE
– Broad spectrum antifungal agent binds to ergosterol
component of fungal cell wall and increases permeability.
Fungocidal. DOC for most progressive, potentially fatal
systemic mycoses (you use this one when the bug is
going to kill the person…)
ADME
– Highly toxic (sterols) (in the bug it breaks down ergosterol
in the cell wall, you have sterols in you, hence, it breaks
down the bugs sterols and can break down your sterols)
– Poor GI absorption - SLOW IV USE ONLY
– Poor CSF
Amphotericin B (cont’d)
Adverse effects – almost 100% - varying
– Phlebitis (slow IV helps prevent this)
– Fever, chills, nausea (common) – pre-treat w/
benadryl / acetaminophen so they don’t suffer so
much
– Nephrotoxicity – residual if 4 g/day, 1 L NS (keep
them hydrated with saline), Monitor urine q 3-4 days
(looking from protein, cast, and serum Creatinine)
– Hypokalemia (lowered potassium)
– Bone marrow suppression (will lower reds, whites,
and browns (platelets))
DD: nephrotoxics - flucytosine
Itraconazole (Sporanox)
MOA / TE
– Azole group of antifungal agents that inhibits
sythesis of ergosterol – fungistatic to treat
histoplamosis, meningitis of cryptococcus
neoformans & disseminated candidiasis
ADME
– PO or IV
– Food  abs. capsules,  abs. of suspension
– Metabolized in liver
– 40% excreted unchanged in urine
Itraconazole (Sporanox) cont’d
Adverse effects
– Common – N, V, and D, rash, HA, edema
– Rare - Hepatic necrosis, transient cardiosuppression
DD
– Inhibits cytochrome P450 isozymes (if system is
impaired, your drug levels are going to rise, will also
raise other drug levels)
– Increases levels of warfarin, digoxin, sulfonylureas
(antidiabetic drug-watch blood sugar), cyclosporine,
quinidine and many other drugs
– Acid reduces decrease drug levels
• Pepsid, prilosec, etc. will impair absorption of Itraconazole
Azoles: Special Considerations
• Fluconazole [Diflucan]
– Lower toxicity level
– Can be taken orally
– SJS syndrome (Steven’s johnson Syndrome
is a side effect of this medication. Looks like a
chemical burn)
• Ketoconazole [Nizoral]
– Effect on sex hormones – inhibits production
(will impair fertility)
Drugs for Superficial Mycoses
• Dermatophytic infections (e.g., ringworm)
– Tinea pedis, tinea corporis, t. cruris, & t. capitis
• Drugs
– Clotrimazole (Gyne-Lotrimin) – DOC for
topical dermatophytic and candida
infections of skin, mouth, vagina
• Vulvovaginal candidiasis
– Griseofulvin (Grifulvin) - oral
• Onychomycosis (fungal infection of the toes
(toenails)
Griseofulvin (Grifulvin V)
MOA / TE
– Superficial mycoses only – inhibits fungal mitosis –
incorporates into keratin (that’s how is suppresses the
bugs)
Adverse effects
– Transient headache, rash, GI upset
– Contraindicated in hepatocellular disease (this is liver
intensive medication, like most of the antifungals)
DD
– Decreases warfarin
Antiviral Agents I:
Drugs for Non-HIV
Viral Infections
Chapter 92
They mutate readily, they live in your cells (so
they’re hard to get to). They are harder to treat
b/c they are harder to target...
Viral Infections
• Dilemma (see previous slide)
• Types
– HSV (Herpes-simplex) More sensitive to
antivirals
• Genitalia, mouth, face (HSV-2)
– VZV (Varicella Zoster) Moderately sensitive to
antivirals. Relative to HSV
• Chicken pox – Shingles
– CMV (Cytomegalovirus) Less sensitive to
antivirals = more resistant
Herpes
• Look in book for some box on herpes.
There is no cure for viral infections like
Herpes. All we can do is treat them an live
around them…
• Just get that the same antivirals are used
over and over again…
Drugs for Non-HIV
Viral Infections
Prototype: Acyclovir [Zovirax]
• MOA / TE: Suppress synthesis of viral DNA
and is useful in treating HSV1,2 & VZV – no
cure
• Adverse Effects
– Intravenous: reversible nephrotoxicity, phlebitis
• Infuse slowly – hydration (trying to protect the
kidneys) – during & 2 hr after
– Oral: GI, vertigo
– Topical: stinging
Acyclovir [Zovirax]
• Nursing Implications
– Resistance – type of clients (seen in just about
everybody that is on the drug long term)
– IV indicated for immunocompromised pt
– STI control (just b/c your partner is on antivirals
doesn’t mean that you won’t get it or that you’re
safe) STI is new acronym for STD (Changed it to
infection)
– Treatment for VZV in elderly and children (w/i 24
hr)
Acyclovir [Zovirax] cont’d
• Nursing Implications (con’td)
– po (low availability), topically or IV
• NO IV bolus (you can’t take a big piece of the drug
and stick it in fast), NO IM, or NO SubQ injections
– Valacyclovir [Valtrex] – prodrug that increases
oral bioavailability (of acyclovir) by 55%
• Without regard to meals
Ganciclovir [Cytovene, Vitrasert]
• MOA / TE
– Suppresses replication of viral DNA to treat CMV retinitis
of immune compromised clients & prevent CMV in
transplant patients
• Adverse effects
– Granulocytopenia (a piece of your wbc’s) &
thrombocytopenia
– Mutagenesis, carcinogenesis
– Teratogenisis and infertility – (90d following cessation)
• valganciclovir (Valcyte) – prodrug for oral use (of
ganciclovir)
– Take intact – with food
Hepatitis C (HCV)
•
•
•
•
•
Transmission—blood and semen
Typically asymptomatic
Leading cause for liver transplants
Among most common causes of liver cancer
Drugs
– Pegylated interferon alfa combined with
ribavirin (Used in combination to treat
HepC)
Interferon alfa (Peg-Intron)
immune modulatory, antineoplastic, antiviral
• MOA / TE
– Blocks entry of virus, synthesis of viral m-RNA and proteins, and
viral assembly. Tx of chronic Hep B (first choice is to vaccinate)
&C
• ADME
– Pegylated - longer acting
– Only parenterally (subQ usually)
• Adverse Effects
– Flu-like (fever, myalgia, HA, fatigue) & depression (makes you
feel real bad)
– Long/High dose – thyroid dysfunction, heart damage, bone
marrow suppression
– Alopecia, GI, injection site pain, bruising
Ribavirin (Rebetol)
• MOA unclear (Goes with Interferon)
– Used with Interferon A - together are DOC for
Hep C (HCV).
– Therapy 24 to 48 weeks. Goal is SVR –
sustained virologic response (loss of
detectable viral RNA)
• Adverse effects
– Hemolytic anemia (anemia due to broken
blood cells)
– Teratogenic (Category X) – two forms of BC
• Dosage based on weight
Hepatitis B - HBV
• Transmission—blood and semen
• Drugs
– HBV vaccine
– Interferon alfa-2b [PEG-Intron]
– Lamivudine [Epivir-HBV] (high resistance)
– Adefovir [Hepsera]
• Duration of treatment and relapse
– They really don’t know yet if it has to be
lifelong… but probably.
Flu Vaccines
• 3 strains – selected by CDC, FDA, & WHO
• Inactivated
– IM
• Live attenuated – LAIV (Flumist) – 2003
– Intranasally
– MUST BE FROZEN
– Only ages 5-49 (r/t to ability to do something
about immune response)
Flu Vaccine (cont)
• Efficacy – Who should receive it? Most
people…
– 1-2 wks & lasts for 6 mo
• Adverse effects
– Fever, malaise, myalgia
– Guillain-Barré syndrome – Swine flu vac. 1976
– LAIV (inhaled version) – runny nose, HA, cough
– rare GBS, anaphylaxis
• Precautions and contraindications
– Acute febrile illness, hypersensitivity to eggs
Flu Vaccine (cont)
• Who should NOT without MD approval?
– Allergy to egg
– Previous severe reaction
– GBS
– Moderate, severe illness w/ fever
– Children under 6 months
– LAIV not for: adults over 50, children under 5,
preggers, children or adolescents on longterm ASA therapy, chronic heart, lung disease
Drugs for Influenza
Prototype: oseltamivir (Tamiflu)
• MOA / TE: inhibit viral replication of Inf A&B and is
used to prevent and treat same – effective if
implemented within 2 days of sxms
• Adverse effects
– N&V
– Confusion, self injury
• Expensive – must be started prior to 48 hr
(must be given quickly or it’s ineffective...)