Antimicrobial Agents: Affect cell walls

Susceptibility of the Body

• Age

  • Children and the elderly

• Exposure to pathogenic organisms

• Disruption of the body’s normal barriers

  • Normal flora is affected

• Inadequate immunological defenses

  • Immunocompromised

• Impaired circulation

• Poor nutritional status

Sources of Infection

• Bacteria

  • One celled organisms

• Fungi

  • Slow growing

    • Candidiasis

    • Systemic mycosis

• Viruses

  • Composed of a nucleus

  • Enter host to reproduce

Chain of Infection

• Infectious Agent

  • Ex. Bacteria

• Reservoir or Source

  • People

  • Water

• Portal of Exit

  • Skin

• Mode of Transmission

  • Airborne

• Portal of Entry

  • Respiratory

• Susceptible host

  • Immunocompromised

Bactericidal

• Cause immediate death

  • Penicillins

  • Cephalosporins

  • Aminoglycosides

Bacteriostatic

• Inhibit the growth of bacteria

  • Sulfonamides

  • Tetracycline

Site of action

• Cell wall synthesis, inhibit protein synthesis, interfere with permeability of cell membrane (amphotericin B)

Narrow spectrum

Limited number of organisms

Broad spectrum

Use when identity of organism has not been established

General Adverse Reactions

• Kidney

  • Drugs metabolized and excreted via the kidneys

  • Aminoglycosides

• GI

  • Stimulate CTZ

• Neurotoxic, Nephrotoxic, Ototoxic

  • Vertigo, dizziness, loss of hearing, elevated serum creatinine and BUN

  • Aminoglycosides

• Liver

  • Cephalosporins

• Hypersensitivity

• Superinfections

  • a secondary infection that occurs during or after an existing primary infection. It is caused by a different microorganism that takes advantage of the weakened immune system or damaged tissues caused by the primary infection.

Prophylaxis

• Traveling

  • Antimalarials

• Surgery

  • Orthopedic

  • GI

  • Cardiac

• Known cardiac disease

  • Congenital

  • Valvular Heart

• Neutropenia

• Recurrent UTI’s

Diagnosis

• Culture and sensitivity

  • Disk diffusion /Kirby-Bauer

• Blood culture

Gram positive

• Streptococcus pneumoniae

• Often aerobic

Gram negative

• Eschericia coli

• Often anaerobic

C & S Apgar Plate

• zone of inhibition

  • Large zone = Antibiotic works (sensitive)

  • Small zone = Antibiotic does NOT work well (resistant)

  • No zone = Completely resistant

7 Drug Considerations

• Identify the pathogen

• Drug susceptibility

  • Look at infection site

  • E. coli---UTI

  • Empiric therapy

  • C &S

• Drug Spectrum

  • Narrowest spectrum.

  • Gram + cocci/bacilli

    • penicillin G and V

    • vancomycin

  • Mycobacterium TB

    • isoniazid

    • Rifampin

• Drug Dose

• Duration

• Site of infection

  • = to or > than the Minimum Inhibitory Concentration (MIC)

• Patient’s Health Status

Antibiotics that Affect the Cell Wall

• penicillins (ampicillin/Pfizerpen)

• cephalosporins (cefazolin/Kefzol or Ancef)

• carbapanems (cilastatin-imipenem/Primaxin)

• vancomycin (Vancocin)

Cell Wall

Maintain internal cellular environment

Resistance

• Drug does not reach binding sites.

• Bacteria produces enzymes that inactivates the drug.

  • penicillinase

  • cephalosporinase

• Resistance occur when bacteria produce enzyme (penicillinase/cephalosporinase) -> cause medication to become inactive so it can’t blind to PBP

  When medication blind to PBP, it can't reach the microorganism / can’t blind to target site

• Penicillin blinding protein (PBP) - Binding  has  to occur to produce antibiotic effects

• Many bacteria are resistant to penicillin

Narrow spectrum penicillins

• penicillin G

  • Pneumococcal

  • Streptococcal

  • Bacterial endocarditis

  • Syphillis

Aminopenicillins (broad)

• ampicillin (P)

• amoxicillin

  • Septiciemia

  • Bacterial meningitis

Extended spectrum

• piperacillin (Pipracil)

  • Lower respiratory tract

Penicillin-Beta Lactamase Inhibitor Combination

• Ampicillin-sulbactam (Unasyn)

• Amoxicillin-clavulanate (Augmentin)

• Piperacillin-tazobactam (Zosyn)

  • Bactericidal

  • Respiratory, pneumonia, blood infections

Penicillanase resistant

• dicloxacillin (oral)

• nafcillin/oxacillin (IV)

Ampicillin Indications:

• Skin

• Soft tissue

• Respiratory

• GI/GU

Ampicillin Contraindications:

• Hypersensitivities

• Allergies (common)

  • Penicillins

  • Cephalosporins

  • Carbapenems

Ampicillin AE

• Adverse Effects:

  • Allergic Rxn

  • Rash

  • Fever

  • Wheezing

  • Anaphylaxis

• GI rxn

  • N/V

  • Diarrhea

  • Gastritis

  • Abdominal Pain

• Other Rxn/s:

  • Glossitis

  • Stomatitis

  • Furry Tongue

  • Oral or vaginal candidiasis

  • Nephropathy

• Superinfection

• Pain/Inflammation at Injection Site

Penicillin G

• Similar adverse effects to ampicillins

• Drug Interactions

  • Concurrent use with tetracyclines

    • Penicillin G Decreased

Penicillin G Indications

• Staph

• Strep

• Meningitis

Penicillin G - Parenteral aminoglycosides inactivated with concurrent use:

• amikacin (Amikin)

• gentamicin (Garamycin)

• kanamicin (Kantrex)

• streptomycin

• tobramycin (Nebcin)

Penicillin G: Probenecid (oral)

IV Penicillin G

High does of penicillin G

• can irritate the CNS.

• CNS toxicity: confusion, lethargy, dysphagia, seizure, coma

Penicillins Nursing Mgmt:

• Rash

• Lesion

• Respiratory Status

• Birth Control

  • Counteracts

  • Back up method

• Pregnant/Lactating

  • Crosses placenta; excreted in breast milk.

• Elderly

  • Reduced dose

• Take around the clock

• Oral prep

  • Empty stomach

  • 1 hour before; 2 hours after

  • Food decreases absorption

• IV

  • Monitor for phlebitis

• IM

  • Aspirate

• Stomatitis

  • Small frequent meals

  • Ice chips

  • Mouth care

• Diarrhea

  • Fluid replacement

• I/O’s

  • Kidney impairment

Penicillins IV

Monitor for phlebitis

Drugs that increase ampicillin effects:

• allopurinol:

• clavulanic acid

• probenecid

• colchicine

allopurinol +ampicillin:

Increases skin rash.

clavulanic acid + ampicillin

Prevents resistance in bacteria that secrete beta lactamase.

probenecid + ampicillin

Prevents renal tubular excretion.

colchicine + ampicillin

Prevents renal excretion

Drugs that decrease the effects of ampicillin:

• chloroquine

• tetracycline

chloroquine + ampicillin

Decreases ampicillin concentration.

tetracycline + ampicillin

Decreases ampicillin’s therapeutic effects.

Carbapenems Drug 1

Cilastatin-imipenem (Primaxin)

Carbapenems Drug 2

ertapenem (Invanz)

Carbapenems Drug 3

meropenem (Merrem)

Carbapenems Drug 4

• Imipenem

  • Broad spectrum

  • Imipenem given with cilastatin to prevent activation of renal dehydropeptidase.

Carbapenems

• Gram + and gram - cocci

  • Bacilli

  • anaerobes

• IV or IM

• Excreted in kidneys

• Beta Lactam Antibiotics

Imipenem

• inactivated by dehydropeptidase; give with cilastatin (dehydropeptidase inhibitor)

• Beta Lactam Antibiotics

Carbapenems AE

• N/V

• Diarrhea

• Rash

• Pruritis

• Superinfections (Candida species)

• Injection site rxns

Carbapenems Contraindications/Precautions:

• Hypersensitivity to penicillin & cephalosporins

• Head trauma

• Brain lesions

• Pre-existing seizures

ertapenem

• IV or IM

• Manages mild to severe abdominal and skin infections.

• Given as a single agent.

• Excreted in kidneys

• Not indicated in children

  • Renal complications

• Secreted in breastmilk

• A/E’s and contraindication similar to imipenem

meropenem

• Manages abdominal infections

  • Appendicitis, peritonitis, resistant nosocomial (HAI)

  • Contraindications: Hypersensitivity

  • Excreted via kidneys unchanged.

  • May interact with valproic acid.

Cephalosporins (5 generations)

• Ist

  • Cefazolin (P) (Kefzol, Ancef)

  • Cephalexin (Keflex)

    • Least activity against gram –

    • Increased gram + coverage

• 2nd

  • cefaclor (Ceclor)

  • cefotetan

• 3rd

  • cefdinir (Omnicef)

  • ceftriaxone (Rocephin)

• 4th

  • cefepime

    • (Maxipime)

      • Most effective against gram –

• 5th

  • ceftaroline (Teflara)

Cephalosporins (1st-5th)

• 1st

  • Gram + staphylococci and streptococci

  • Not affected by food; take with food to decrease GI upset.

• 2nd

  • Broader coverage against gram – than 1st

  • Lower respiratory tract

  • Haemophilus influenzae

  • Otitis, sinusitis

• 3rd

  • Effective against gram –

  • Penetrates CSF

    • Meningitis

  • E coli.

  • Serratia marsesans

• 4th

  • Gram + and –

    • Tx resistant 3rd generation infections P aeruginosa

• 5th

  • IV

  • Used for hospital acquired infections

  • MRSA, VRSA

Cephalosporins

• Similar to PCN’s

• Broad spectrum

• Low toxicity

cefazolin (Ancef, Kefzol)

• Used on many infections

  • Skin, bone, blood, respiratory tract.

  • Resp:S pneumoniae

  • Skin: S aureus

  • GI: E. coli

• Does not cross BBB; crosses placenta/breastmilk

• False positive urine glucose

Cephalosporins Admin:

• IV/IM

• Oral: Ist generation

  • cephalexin; cefadroxil

Cepahlosporins AE

• Well tolerated

• Abdominal pain

• N/V, Diarrhea

• Allergic rxs:

  • Hypersensitivity

  • Maculopapular rash

  • Bronchospasms/anaphylaxis

    • Severe, but rare. Treat with respiratory support/epinephrine.

• Bleeding

  • Cefotetan

• Thrombophlebitis

  • May occur with IV infusions

Cephalosporins Nursing Mgmt:

• Similar to penicillins

• Caution with elderly

• Pregnancy

• Lactation

• Assess alcohol use

  • Cefotetan

• Check IV site for phlebitis

• Review C and S

• Round the clock dosing

• Take with food or fluids to decrease GI complications

• Small, frequent meals, ice chips, mouth care

• Hydration status

• Disulfiram Effect

Cepahlosporins Drug Interactions

• Combination therapy,

  • Aminoglycoside/cephalosporin

    • Look for nephrotoxicity

    • BUN

    • Creatinine

    • I/O’s

• Anticoagulants

  • Bleeding gums/bruised skin

• Probenecid

• Refrain from drinking 72 hours after drug has stopped.

  • disulfiram rxn

Cephalosporins Nursing Mgmt: More

• Watch out for decreased prothrombin activity

• Assess for rash

• Do not mix ceftriaxone and IV soln’s with calcium

  • Cause precipitate

• Take full dose

Vancomycin MOA

• Time dependent antibiotic that inhibits cell wall synthesis.

  • Excreted in kidneys

• Beta lacmin ring – don’t have

Vancomycin

• Toxic effects

  • Limited use.

• Works on gram +

  • VRE problematic

  • To decrease VRE risk, CDC recommends limiting use.

Vancomycin TX

• Bacterial septiciemia

• Pseudomembranous colitis caused by Clostridium dificile.

• S. aureus

• MRSA

Vancomycin (MORE)

• Oral bioavailability low: IV

• Plasma conc peaks in 1 hour

  • Give infusions slowly over 1 to 2 hours to avoid hypotension, flushing, and skin rash

Vancomycin Contraindications

• Hypersensitivity

• Pregnancy

• Renal disease

• Concomitant aminoglycoside use

  • Nephrotoxic

Vancomycin AE

• Ototoxicity; > 30 mcg/ml

• Nephrotoxicity

  • Decreased incidence

  • Check renal function

  • Very toxicity to kidney

  • Check creatinine and BUN

Vancomycin S/S

• Fever

• Chills

• Sinus tach

• Parathesias

• Phlebitis

• Flushing

  • Face, neck, upper body, arms, back

  • Red Man’s Syndrome

    • Histamine release resulting in anaphylaxis.

    • Red man syndrome – histamine release too much -> release when IV/infusion too fast

Vancomycin Nursing Mgmt:

• Assess contraindications

  • Renal patients

• Nephrotoxic/Ototoxic drugs

  • I/O’s

  • Toxicity; conc > above 60 to 80 mcg/ml

    • Ataxia; nystagmus

• Divided doses around the clock.

• C/S Testing

• Monitor for superinfection

Vancomycin Admin

• Admin IV over 60 minutes

• Diminished flushing, tachycardia, hypotension, rashes.

• Diminished phlebitis risk

• Avoid extravasation

  • Extravasation - the leakage of fluid, such as blood, lymph, or medication, from a blood vessel into the surrounding tissues

• Peak:

  • 1 hour completion

• Trough

  • 30 minutes prior