ANTIINFECTIVE Agents

Fall 2013
Wilhelmina Rich MSN, RN
Terminology
Sterilization
Sanitization
Germicide/bactericidal
Bacteriostatic
Chemotherapy, antibiotic & antimicrobial
Selective toxicity
Antiseptic vs Disinfectant
Antiseptic: agents applied to living tissue.
Useful as prophylaxis, wound cleansing
Alcohol, iodine preparations, chlorine, phenolic
Disinfectant: applied to inanimate objects
Aldehydes
Povidone iodine
Sodium hypochlorite
Hydrogen peroxide
Alcohols
Antiseptic
Ethanol: virucide; bactericidal; should not be applied to open wound
Isopropanol:@ 70% concentration more germicidal than ethanol; promotes local vasodilation
Aldehydes
Disinfection
Glutaraldehyde[cidex]: lethal to all microorganisms; fumes irritate respiratory tract
Formaldehyde: slower acting and more irritating
Iodines
Germicidal
Solution & tinctures: tinctures contain ethanol
Povidone: less effective than other iodine preparations; primarily prophylaxis
Chlorine compounds
Oxychlorosene sodium: used as a topical antiseptic; esp. useful in drug resistant microbes
Sodium hypochlorite: unstable and solutions must be prepared fresh for each use
Phenols
Hexachlorophene [pHisoHex & Septisol]: bacteriostatic; non-effective on gram negative bacteria; can be
absorbed thru skin
Miscellaneous agents
Hydrogen peroxide: excellent disinfectant & sterilizing agent
Chlorhexidine[Hibiclens]: important surgical antiseptic
Antibiotic/Antimicrobial Agents
Classification by Susceptible Organisms
Gram negative & gram positive microbes
Anaerobic and aerobic microbes
Selective toxicity options
Disruptions of bacterial cell wall
Inhibition of enzyme unique to bacteria
Disruption of bacterial protein synthesis
Mechanisms of action
Inhibit bacterial cell wall synthesis or activate enzymes that disrupt cell wall : penicillins, cephalosporins
Increase cell membrane permeability: antifungals
Cause lethal inhibition of bacterial protein synthesis: aminoglycosides
mechanisms
Nonlethal inhibitions of bacterial protein synthesis: tetracyclines
Inhibit bacterial synthesis of nucleic acids:fluoroquinolones, rifampin
Antimetabolites :sulfonamides
Inhibitors of viral enzymes: protease inhibitors, nucleosides analogs
Antibiotics: factors affecting outcome of therapy
Resistance to antibiotics
Identifying causative bacteria
Site of infection
Other drugs
Clinical status of patient
Problems in antibiotic therapy
Direct toxicity
Allergic reactions
Superinfections
Viral infections
Early discontinuation
Instability of stored antibiotics
Potential dangers to children
Beta-Lactam antibiotics
Effective against most commonly encountered pathogens
Penicillins, carbapenems, monobactams & cephalosporins
Bactericidal drugs most effective against actively multiplying bacteria
Resistance develops; beta-lactamase
Excreted renally
Penicillin G & Penicillin V
Does not cross brain-blood barrier unless there is inflammation
Highly active against gram + & gram - cocci
Allergies most common adverse reactions; GI distress 2nd common reaction
Cross sensitivity to cephalosporins
Direct drug toxicity is low

Procaine Penicillin G
Designed for slow absorption from IM sites. Must be given deep IM
Used in mild to mod.serious infections or when prophylaxis is required.
ADR with CNS usually transient.
Penicillin V can be given PO on an empty stomach.
Aminopenicillins
Ampicillin and amoxicillin
Broader spectrum than natural & penicillinase-resistant
Ineffective against most staph
Used to Rx gonococcal infection, URI,UTI, & otitis media, gram negative
Pregnancy B
Extended- spectrum PCN
Used to treat serious infections caused by gram negative organisms.
Hypersensitivity can occur

All inhibit platelet aggregation.
Pregnancy category B; cross placenta & excreted in breast milk
Major Nursing Implications
Take samples for culture before initiation of treatment
Identify high-risk clients
Take 1 hour ac or 2 hr pc
Monitor kidney function
Minimize adverse effects

Carbapenems
Bactericidal and inhibits cell wall synthesis.
Reserved for complicated body cavity and connective tissue infections.
Small risk of cross allergenicity and seizures.
Example: Primaxin/imipenem
monobactams
Able to preserve normal gram positive and anaerobic flora.
Lacks cross-allergenicity with PCN
Similar to aminoglycosides.
Ex: aztreonan/Azactam
Cephalosporins
Bactericidal
All are active against most gram positive cocci & many gram negative bacilli.
Chemical structure similar to PCN
Cross sensitivity with PCNs (10%)

The higher the generation:
(1)the better they treat gram negative bacteria & anaerobes,
-lactamases, gram negative actions
ative

continued
1st generation: cefazolin/ancef, cephalexin/keflex
2nd: cefoxitin/mefoxin
3rd: ceftazidime/fortaz, ceftriaxone/rocephin
4th:cefepime/maxipime
Drug interactions: Probenecid, alcohol, aminoglycosides
Precautions
Major care implications
Identify high-risk clients
Advise pt to take oral cephalosporins with food if gastric upset occurs
Refrigerate oral suspensions
Minimize adverse effects
Minimize adverse interactions
Macrolides
Bacteriostatic in low concentration, bactericidal in higher concentration
Devoid of serious toxicity when used alone.
Protein bound. Hepatic elimination
Erythromycin, clarithromycin, dirithromycin and azithromycin
Erythromycin one of safest antibiotics
Erythromycin
Rx of 1st choice
Alternative PCN G in those allergic to PCNs.
Given prophylactically before dental procedures
Crosses placenta but adverse effects in fetus not observed.
S/E: GI tract complaints; superinfection of bowel; thrombophlebitis if given IV
sient hearing impairment.
Allergic reaction rare.


Azithromycin & Clarithromycin
Zithromax
Excellent tissue penetration
Long duration of action=dosing qd
Food decreases rate and extent of GI absorption
Used in MAC

Biaxin
PO bid
Can be given with or without food
Used in MAC
Used in combination to treat Heliocobacter pylori
Tetracyclines
DOC for treatment of rickettsial diseases, chlamydial infections, peptic ulcer disease, acne
Should not be given with calcium supplements, milk products, iron supplements, Mg laxatives, and most
antacid
Crosses placenta & enters fetal circulation
GI irritation, discolors permanent teeth, superinfection, hepatoxicity, renal toxicity
Doxycycline/Vibramycin: travelers diarrhea

Major care implications
Advise client to take on an empty stomach and full glass of water
Minimize adverse effects
Minimize adverse interactions
Aminogylcosides
Narrow spectrum used primarily against aerobic gram negative bacilli
Not absorbed from GI tract, does not cross BBB, & excreted rapidly by kidney
Neomycin only topical in group
Adverse effects of ototoxicity, nephrotoxicity, neuromuscular blockade, hypersensitivity
Peak & trough level
Gentamicin, tobramycin, amikacin, kanaycin, streptomycin




Parenteral therapy-Rx of serious infections caused by gram negative
Oral therapy-suppression of bowel flora
prior to elective colorectal surgery
Topical therapy- Rx of local infections of the eyes, ears, and skin



Major care implications
Intravenous infusions should be given slowly (30+ min)
Monitor aminoglycoside levels
Minimize adverse effects
Minimize adverse interactions
Fluoroquinolones
Bacteriocidal & used for growing bacteria
Good for gram negative more than positive
Can cause tendon rupture
Ciprofloxacin good against P. aeruginosa, many anarobic, UTI, bone joint, and skin infections, infectious
diarrhea, gonococcal infections



Crystalluria occurs @ high doses in alkaline pH.


ceiving warfarin


Sulfonamides
Bacteriostatic; well absorbed & distributed; crosses to placenta
Preferred drugs for acute UTI caused by E. coli & chronic upper URI
Metabolized in the liver, excreted by kidneys
Hypersensitivity reactions, blood dyscrasias, kernicterus, crystalluria, photosensitivity

Sulfadiazine treats toxoplamosis
Sulfamethoxazole/bactrim treat UTI,P.carinii, resp infections, gonococcal urethritis
Sulfisoxazole/gantrisin

Nursing Implications
Identify hi-risk pts
Take oral sulfonamides on empty stomach & full glass of water
Discont drug @ 1st sign of hypersensitivity
Avoid prolonged exposure to sunlight
Periodic blood cell counts
Do not give to pregnant or infants under age 2 mos
Miscellaneous antibiotics
Chloamphenicol: used infections that cant be treated with other antibiotic. Bone marrow suppression;
gray-baby syndrome; otic neuritis
Vancomycin: destroys most gram +ive MRSA. Useful in pt allergic PCN and cephalosporins. Not
absorbed after PO & not useful for systemic infections. Red mans syndrome. Ototoxicity &
nephrotoxicity

Miscellaneous
Clindamycin/cleocin:
useful in anaerobic infections; pseudomembrane colitis major adverse effect

Flagyl/metronidazole:
Effective against protozoal infections
Good activity against anaerobic organism
Acute drug interactions with alcohol, lithium, benzodiazepams
Antituberculosis Agents
Tuberculosis
Many be limited to lungs or become disseminated
Screening: PPD, chest x-ray, sputum
Drug resistance due to inadequate drug therapy
Preventive therapy
Therapy 6 months to 2+years.
Primary drugs
Isoniazid[INH]: bactericidal; blocks vitamin B6 myobacteria rapidly acquire resistance to drug.
Considered the most useful antiTB agent. Used alone for prophylaxis. Peripheral neuropathy most
common adverse reaction. Hepatotoxicity most serious side effect.

Cont
Rifampin causes GI tract upset & rashes. Turns body fluid orange-red color. Liver abnormalities may
occur. Given with INH. Use of alcohol increases risk of drug-induced hepatitis.
Pyrazinamide[PZA]: rapidly & completely absorbed orally, distributed freely to most tissues. Effective
only against mycobacteria. Often causes joint pain. No contraindications
Cont
Ethambutol: bacteriostatic; weel absorbed; effective only against mycobacteria. Can cause optic neuritis
Streptomycin: Resistance develops quickly if used alone. IM only. Adverse reactions same as other
aminogylcisides.
Secondary drugs
Capreomycin, para-aminosalicyclic acid[PAS],cycloserine, kanamycin & ethionamide
Generally less effective & more toxic than 1st line drugs
Used to treat severe pulm TB and disseminated infection.
Always employed in conjunction with 1st line drug.
Major Care Implications
Evaluating treatment
Identifying high risk clients
Administration of 1st line meds
Minimizing adverse effects of 1st line meds
Minimizing adverse interactions of 1st line meds
Antifungal Agents
Systemic and superficial mycoses
Amphotericin B
Fungicidal & fungistatic effective in Rx of systemic fungal infections in immunocompromised pts
Nephrotoxicity occurs in most
Adverse CNS effects
Fluconazole/Diflucan
PO or IV
Can cause GI distrubances & increase serum aminotransferase.
Effective against systemic & CNS candida & cryptococcus
Nystatin
Similar structure & mechaism as amphotericin
Used as topical agent in vagina & oral candida infections.
PO forms causes GI distress
Nursing Implications
Infusion reactions with amphotericin B
Amphotericin B should not be combined with other nephrotoxic drugs.
Administration of nystatin suspension
Antiprotozoal & Antihelmintics
Antiprotozoal
Antimalarial therapy based on life cycle of protozoa. Objectives are (1) treat acute attack, (2) prevent
relapse, & (3) prophylaxis.
Amebicides & trichomonacides used for amebiasis, giardiasis, & trichomoniasis which are the most
common protozoal infections in USA.
Antimalarial
Cloroquine suppresses malaria symptoms & terminates acute malarial attack of both types of infection.
Concentrated in liver. Visual disturbances, headache, skin rash and GI distress.
Primaquine:curative for relapses & to prevent malaria in exposed clients. May cause hemolytic anemia
Ambecides & trichomonacides
Metronidazole/flagyl: doc for symptomatic intestinal & systemic amebiasis. Effective against
trichomoniasis in males & females, and giardiasis. Many anaerobic bacteria also sensitive. Avoid
alcohol.

Cont
Pentamidine: primary drug for Pneumocystis carinii pneumonia. Aerosol treatments for prophylaxis.
Adverse reactions with IV route which is route for acute disease control.
Antihelmintics
Roundworms may infest intestinal lumen or inhabit tissues
Tapeworms acquired by eating undercooked beef,pork or fish
Flukes are ingested from infected organ meats or snails.


Agents differ in antiparasitic spectra
Important to identify organism
Mebendazole: broad-spectrum; oral use for intestinal helmiths. Fatty foods favor absorption. Few toxic
reactions. Superinfections can occur. Assess stooling.


Care Implications for protozoal & helminthic infestations
Treatment of entire family
Not recommendedfor use during pregnancy.
Preventative malaria actions.
Assessment of affective tissue
Anti-Infective: Antiviral Agents
Selected Viral Infections
Avian Influenza A(H5N1)
Herpesvirus: cytomegalovirus infection and retinitis; genital herpes; herpes zoster; Epstein-Barr
Human immunodeficiency virus
Human papilloma virus
Respiratory Syncytial Virus
Viral hepatitis: HAV, HBV, HCV

Viremic Spread
DNA viruses
Herpes simplex 1 &2, Varicella-zoster virus and cytomegalovirus
Host cells encoded for new viruses and viral DNA incorporated in hosts daughter cells
RNA viruses
HIV
Viral RNA converted to DNA by enyme reverse transcriptase before replication can occur
Viremic Spread in Man
Primary site of infection no symptoms with replications
Bloodstream primary viremia has no symptoms
2nd sites of infection replication may produce mild symptoms
Bloodstream rash, fever or chills, severity dependent on # of viruses released
CNS rarely involved but infections are serious
General principles of treatment
Some viral infections are self-limiting.
Drug therapy may not be warranted due to expense and possible adverse effects worse than symptoms.
Antiviral is targeted to a specific structure within the virus.
Enhancement of immune system-system-immunomodulators.
Prevention thru vaccines
Antivirals remain least effective of all anti-infective classes.



Non-HIV Antiviral Drugs
Herpes and Cytomegalo-viruses anti-viral agents
Acyclovir
Herpes Simplex Virus most sensitive, varicella zoster mod sensitive, most strains of cytomegalovirus is
resistant
Resistant rare in immunocompetent
Renal excretion with half-life of 2.5 hr. Crosses blood-brain barrier
IV well tolerated. Nephrotoxicity reversible.
PO reactions of nausea, vomit-ing,diarrhea, HA & vertigo. Topical stinging sensation
Nursing implications
Assess for GI symptoms, skin rashes & CNS side effects.
Pt should be well hydrated during IV infusions.
Driving or operating hazardous equipment warning
Use gloves when applying topical agents.
Educate client that med will not cure or prevent spread of herpes.
Regular Pap smears
Influenza Prophylaxis
Symmetral/amantadine
Useful in high-risk pts.
Cross-resistance between them
Crosses blood-brain barrier
Side effects mainly CNS
Used with caution in pregnancy & nursing mothers
Rx of parkinsonism

rimantadine
Useful in high-risk pts.
Cross-resistance between them
Used with caution in pregnancy & nursing mothers
Metabolized in liver
S/E: GI, CNS toxicity, insomnia, dizziness, headache.
Neuraminidase inhibitors
Tamiflu/oseltamivir
PO only
Prophylaxis & treatment
Adverse effects of nausea and vomiting
Relenza/zanamivir
Inhalation route
Indicated for treatment of active illness
Adverse effects of nausea, diarrhea and sinusitis
Respiratory Syncytial Virus
Ribavirn: effective broad spectrum
Rhinoviruses & enteroviruses relatively resistant to it.
Used to treat infants & young children infected with severe RSV.
Aerosal route safer then oral or intravenous
Tetragenic
Avoid contact with drug if possible, may cause eye irritation or headaches

Drug classes for Viral Hepatitis Infections
Vaccines [A,B] are preventive
Interferons
Nucleoside Reverse Transcriptase Inhibitors [NRTI]: lamivudine/Epivir
Oral
Side effects: GI, lactic acidosis
Category C