Anti-infective DrugsJan Bazner-ChandlerMSN, CNS, RN, CPNP

Bacteria

BacteriaGram-positive bacterium has a thick layer of peptioglycan.Gram-negative bacterium has a thin peptioglycan layer and an outer membrane.

Common Bacterial PathogensGram positive Staphylococcus aureus StreptocciEnterococciGram negative Escherichia coli or E-coliKlebsiellaProteusPseudomonas

Empiric TherapyAdministration of antibiotics based on the practitioners judgment of the pathogens most likely to be causing the infection; it involves the presumptive treatment of an infection to avoid treatment delay before specific cuture information has been obtained.

Prophylactic Antibiotic TherapyAntibiotics taken before anticipated exposure to an infectious organism in an effort to prevent the development of infection.IV antibiotics given prior to surgery

SuperinfectionAn infection occurring during antimicrobial treatment for another infection, resulting from overgrowth of an organism not susceptible to the antibiotic used.A secondary infection that occurs due weakening of the patients immune system by the first infection.

Examples of SuperinfectionsFungal or yeast infectionDiarrhea due to diminished normal flora of the gastrointestinal tract.

Laboratory TestsGram stain microscopic identification of organism Culture identifies causative agent and susceptibility to specific antibiotics Serology titers or antibodies measured CBC looking at WBC

CulturesThroatWoundUrine Sputum Blood

Clinical PearlAlways collect culture: urine, sputum, wound drainage, or blood prior to starting antibiotic therapy.If technician is drawing blood make sure it has been done before starting antibiotics.

AntimicrobialsDrugs used to prevent or treat infection caused by pathogens

Two ClassificationsBactericidal drugs kill bacteria directly.Bacteriostatic drugs prevent bacteria from dividing or inhibits their growth.

Two Types of BacteriaAerobic grow and live in presence of oxygenStaph & StrepAnaerobic cannot grow in presence of oxygen Deep woundsCharacterized by abscess formation, foul-smelling pus and tissue destruction

Community-Acquired InfectionLess severe and easier to treat, although drug resistant strains are increasingRemember Staph is everywhere it is normal flora on skin and in the upper respiratory tract MRSA: methicillin-resistant-Staphylococcus aureus

Nosocomial InfectionsMore severe and difficult to manage because they often result from drug-resistant microorganisms and occur in clients whose resistance is impairedPseudomonasProteus

Bacterial ResistanceBacteria develop the ability to produce substances which block the action of antibiotics or change their target or ability to penetrate the cells.

What causes resistance?Widespread use of antimicrobial drug Interrupted or inadequate antimicrobial treatment of infectionType of bacteria gram-negative strains have higher rates of resistance Re-occurring infections Condition of the hostLocation critical care areas

Opportunistic HostCompromised immune systemInfantsGeriatric populationCancerHIV positive low T-cell countBurnsSkin breakdownClient with total knee or hip replacement

Client History / Assessment Allergies Previous drug reactionsBaseline renal and liver functionReview culture reports for appropriate antibacterial drug choicePatient response to antibiotics therapyAre they getting better?Any side effects?

AntibioticsSulfonamidesPenicillinsCephalosporinsMacrolidesFluoroquinolonesAminoglycosidesTetracyclines

SulfonamidesAction: inhibit the growth of bacteria (bacteriostatic antibiotic) by inhibiting the growth of susceptible bacteria by preventing bacterial synthesis of folic acid.Usually used in combination drugs.Trimethoprim / sulfamethoxazole: Trade name Bactrim, Septra, TMP/SMX

IndicationsBroad spectrum: can be used against gram negative and gram positive organismsVery useful in treating kidney infections since they achieve a high concentration in the kidneys.Susceptible organisms: Enterobacter, E.Coli, Klebsiella, ProteusProblem: organisms becoming more resistant

Specific Use of Sulfa DrugsHIV patients with pneumocystis cariniiMay be given Bactrim or Septra prophylactically.

ContraindicationsDrug allergy to sulfaUse of thiazide and loop diureticsPregnant women Infants younger than 2 months of age

Adverse EffectsMost common is cutaneous reactions can occur weeks after therapy started. Erythema multiforme (Stevens Johnson Syndrome)Toxic epidermal necrolysis Photosensitivity reactions: exposure to sunlight can result in severe sunburn

B-Lactam AntibioticsIncludes 4 major drug classificationspenicillinscephalosporinscarbapenesmonobactams

PenicillinDerived from mold fungus

Penicillin

First generation IM or IV Newer penicillins have been developed that increase gastric acid stability of penicillin Good drug since it enters most bodily fluids: joint, pleural, and pericardial.Not effective against intraocular (eye) or cerebral spinal fluid infection (CSF)

Penicillin Bactericidal action against sensitive bacteriaAction: binds to bacterial wall, resulting in cell death

Susceptible BacteriaGram-positive organismsStreptococcusEnterococcusStaphylococcus

Adverse ReactionsMost common reaction is GI (diarrhea) when administered orally.Urticaria (rash), pruritus (itching), and angioedema (swelling of the throat)Severe reaction: Stevens Johns SyndromeNote: when giving IV or IM observe for to 1 hour after giving for adverse reactions.

Hives

Anaphylaxis

Combination Penicillin / B-lactamasesUnasynAugmentin TimentinZosyn

Ampicillin Synthetic PenicillinBroad spectrum effective against several gram-positive and gram-negative bacteriaE-coli, proteus, Salmonella, ShigellaNot effective against staphylococci on gonococciBronchitis, sinusitis, and otitis media

Ampicillin Bactericidal action spectrum is broader than penicillin Binds to bacterial wall resulting in cell death

Nursing ImplicationsSame as penicillinAsk client about oral contraceptive use drug may cause transient decrease in effectiveness Advise to use additional BC barrier protection during antibiotic therapy

Amoxicillin Trade name: Amoxil, Trimox, WymoxClassification: aminopenicillinsIndications: skin infections, otitis media (ear infection), sinusitis, respiratory infections.Inexpensive in generic form but required frequent dosing (q 8 hours)

Amoxicillin Oral equivalent of AmpicillinReadily absorbed and reaches therapeutic levels rapidlyDrug of choice in prevention of bacterial endocarditis Clients with total knee or hip replacement, heart valve replacement need to take prior to any dental work, endoscopy exams

Dosing for AmoxicillinAdults: 250 to 500 mg q8hInfants and children less than 20 kg:20 40 mg / kg / day divided into doses q 8 hours

Cephalosporins Widely used drug derived from fungusUsed against gramnegative bacteriaWidely absorbed and distributed in most bodily fluids placenta and breast milk

Cephalosporin First generation Cephalosporin drugs do not reach therapeutic levels in CSF (cerebral spinal fluid) but 2nd, and 3rd generation drugs do especially important in treating meningitis.

Meningitis

First Generation Cephalosporins

Bactericidal action binds to bacterial cell wall, causing cell deathKeflex (PO) still used extensively in treatment of skin infectionsAncef often ordered preoperatively

Impetigo

First Generation Cephalosporins

Bactericidal action binds to bacterial cell wall, causing cell deathKeflex (PO) still used extensively in treatment of skin infectionsAncef often ordered preoperatively in clients undergoing orthopedic procedures

Keflex First generation cephalosporinAction: binds to bacterial cell wall membrane, causing cell deathTherapeutic effect: bactericidal action against susceptible bacteriaActive against many gram-positive cocci step and staph

Client teachingMay be taken with or without food but food may minimize the GI irritation Distribution: may cross placenta or enter breast milk in low concentrations.Excreted entirely by the kidneys.

Keflex DosingAdults: 250 500 mg q 6 hoursChildren: 25 50 mg / kg / day in divided doses q 6 h

Cefazolin or AncefCefazolin first generation cephalosporinWell absorbed following IM or IV administrationCrosses to placenta and breast milk in small concentrationsMinimal CSF penetrationExcreted by kidneys

Knee or hip replacement

Ancef DosingIVUsed for UTI, bone and skin infections, endocarditisNot suitable for treatment of meningitisPerioperative prophylaxis1 gram within 60 minutes of incisionPost operatively every 8 hours for 24 hours (3 doses)

Second-Generation Cephalosporins More active against some gram-negative organisms and anaerobic organisms than the first generation drugs.May be effective in infections resistant to other antibioticsPenetration into CSF is poor but adequate to be used in meningitis Action: bactericidal binds to cell wall

Third Generation Cephalosporin DrugsSimilar to the second generation but has increased activity against gram-negative pathogens even for drug resistant pathogens.CSF penetration is better than the first two generation cephalosporin drugs.

Drug / Drug AllergiesIf a client is allergic to penicillin there is a 1 to 18% chance they will be allergic to cephalosporin drugs.

CarbapenemsHas very broad antibacterial actionAre often used for complicated body cavity and connective tissue infections in the hospitalized patient.imipenem-cilastatin (Primaxin)meropenen (Merrem): only drug in this class used in the treatment of bacterial meningitis.

MacrolidesMacrolides first developed in the 1950s with the drug: erythromycin.Four main drugsazithromycin * ZithromaxClarithromcin * Biaxin dirithromycinerythromycin

MacrolidesTwo of the new drugs in the macrolide classification: azithromycin and clarithromycin have longer duration and improved resistance to acid degradation in the stomach.Dosing is less frequentGI effects decreasedBetter absorption than erythromycin

MacrolidesAction: work by inhibiting protein synthesis in susceptible bacteria.Contraindications: drug allergyAdverse effect: new drugs have lower GI effects and are used in patients allergic to penicillin / cephalosporin drugs.

KetaloidsOnly one drug in this drug classificationGeneric: telithromycinTrade: KetekAvailable for oral use only.Better acid stability and antibacterial coverage than macrolides.

TetracyclinesAction: binds to divalent (Ca2 + mg2) and Al3 mettalic ions to form insoluble complexes.Why do you need to know this? When given with milk, antacids or iron there is a reduction in oral absorption.Contraindicated in children under 8 years of age because it can result in tooth discoloration.

TetracyclinesWhen used? Syphilis and Lyme disease

Antibiotics Used to Treat Serious InfectionsIM or IV administrationHave more toxic side effectsBlood levels may need to be monitored to determine therapeutic versus toxic levels of mediation in the blood.

Serious Adverse EffectsNephrotoxicity: Toxicity to kidneys, often drug induced and manifesting in compromised kidney function.Ototoxicity: Toxicity to the ears, often drug-induced and manifested by varying degrees of hearing loss than is likely to be permanent.Pseudomembranous colitis: a necrotizing, inflammatory bowel condition associated with antibiotic therapy.

AminoglycosidesPharmacologic classification: Bactericidal drugsTherapeutic classification: anti-infectiveAction: inhibits protein synthesis at the level of the 30s ribosome Work primarily on dosing due to concentration dependent killing of bacteria

Concentration Dependent A property of some antibiotics, especially aminoglycosides and vancomycin, of achieving a relatively, high plasma drug concentration, results in the most effective bacterial kill.

Blood Plasma LevelsPeak levels: refers to amount of drug present in blood plasma within 15 to 30 minutes of IV drug administration30 to 90 minutes of IM drug administrationTrough levels: refers to lowest level of drug present in the blood plasma. Since the drugs can cause severe adverse effects the excretion of the drug needs to be monitored.Blood drawn just before the next dose given.

Adverse Effects AminoglycosidesNephrotoxicity occurs in 5 to 25% and ototoxicity (damage to VIII cranial nerve) occurs in 3 to 14%.

Aminoglycosidesgentamicin (Garamycin)tobramycin (Nobcin, TOBI)neomycin (Neo-Fradin) used to irrigate bowel before major bowel surgeryTopical applied to eye and skin infections

Floroquinolones Action: destroys bacteria by altering their DNA.Two most common drugs: ciproflxcin (Cipro) clindamycin (Cleocin)Used in treatment of chronic infections or deep (anaerobic) abdominal infections and MRSA.

Major Adverse Side EffectClindamycin or Cleocin can cause pseudomembranous colitisSigns and symptoms: abdominal pain and diarrhea

MRSA InfectionsMRSA infection is caused by Staphylococcus aureus bacteria often called "staph." MRSA stands for methicillin-resistant Staphylococcus aureus. It's a strain of staph that's resistant to the broad-spectrum antibiotics commonly used to treat it. MRSA can be fatal.

MRSA

Vancomycin Action: destroys bacteria by binding to the bacterial cell wall, producing immediate inhibition of cell wall synthesis and death.One of the drugs used in MRSA infections that are resistant to floroquinolones (cleocin).

Adverse EffectRed man syndrome has often been associated with rapid infusion of the first dose of the drug and was initially attributed to impurities found in vancomycin preparations. Even after improvement in vancomycin's purity, however, reports of the syndrome persist. Flushing on upper chest, neck and faceIntervention: slow the IV infusion rate.

Drugs to help with the FluTamiflu and RelenzaUses: active against influenza virus types A and B.Shown to reduce the duration of influenza infection by a few days.

Anti-viral DrugsKill or suppress viruses by either destroying virons or inhibiting their ability to replicate.Does not irradicate the virus but helps the immune system to eliminate the virus.

Herpes ZosterHerpes simplex virus type 1: cold soreHerpes simplex virus type 2: genital herpesHuman herpesvirus type 3: chicken pox or shingles Human herpesvirus type 4: Espstein Barr VirusHuman herpesvirus type 5: CMV or cytomegalovirus

Cold Sore

Herpes Zoster - Shingles

Herpes DrugsGeneric: acyclovirTrade: ZoviraxAction: interferes with DNA synthesis.Therapeutic effects: Inhibition of viral replication, decreased viral shedding and reduced time for healing of lesions.

acyclovirComes in topical, po and IV preparationsShould be started within 24 hours of outbreak.