Antimicrobial Basics + Antibiotics

antimicrobial (anti-infective)

• work on many different organisms

• bacteria, viruses, fungal, protozoa, helminths

• natural, synthetic, semi-synthetic

antibiotic

subcategory of antimicrobial that can kill or inhibit growth of bacteria

two types of antibiotics

bacteriostatic, bactericidal

bacteriostatic

meds that slow or inhibit bacterial growth

bactericidal

meds that kill bacteria

broad spectrum

• often used first when don’t know what bacteria is

• effective against many organisms, both gram + and gram -

• don’t know what specific organism is

narrow spectrum

• effective against few species of organisms, usually gram + OR gram -

• know organism and sensitivity of pattern

selective toxicity

toxic to specific cells while sparing other cells in close proximity

resistance

• ability of organism to survive against and antimicrobial or render it ineffective

• innate or acquired

• if gram - bacteria, gram + med won’t work

super infection

• occurs because of/during treatment of a primary infection

• second infection superimposed on an earlier infection

  • different microbe

  • resistant microbe

• ex. C. diff

prophylactic antibiotic use

• prevent infection from occuring

• when high risk of infection

  • surgical procedures: orthopedic, cardiac, abdominal

  • dental procedures in pts at risk for endocarditis

    • prosthetic valve, hip/knee replacement

  • immunocompromised

    • neutropenia: HIV, chemo, immunosuppression

opportunistic infection

• ex. C-diff

• organism takes advantage of opp. that usually isn’t there

  • weakened immune system, altered microbiome, breached integumentary barriers

• organisms cause no infection in healthy host

• some organisms live as commensals

  • symbiotic relatinship

in order to cause infection, and organism must…

get by body’s defense mechanisms

innate immunity

all defenses we possess to prevent in organism from invading the body

adaptive immunity

• ability to recognize organisms and attack with specialized cells

• can be gained via vaccines

organism entry areas

• oro/nasopharynx: bronchial airways, lungs, stomach, GIT

• disruption in barrier (skin)

• genitourinary tract

how organisms enter the body

move from non-sterile site to sterile site

translocation

• movement of bacteria across the intestinal lining

  • into peritoneal cavity

  • into blood

blood-blood transfusion

blood transfusions, needle stick

maternal-fetal transmission

• cross placental barrier and directly infect the baby

• during birth

stages of infection

incubation, prodromal, acute, decline, convalescent, resolution

incubation

time from exposure to onset of symptoms

prodromal

after incubation and before ‘characteristic’ symptoms occur

acute

clinical disease symptoms apparent

decline

immune system responds and symptoms gradually improve

convalescent

symptoms resolve and person can return to normal function

resolution

gone

infectious process: injury

• injury

• short period of vasoconstriction

  • helps stop bleeding and prevent invading organisms moving beyond injury site

• then prolonged vasodilation

  • increased blood flow to area, bring immune cells to area

  • contributes to inflammation symptoms

infectious process: increased permeability

• fluid pushed out of vascular space

• fluid moves to exact area of injury

• WBCs get to infection area

• causes edema and swelling

infectious process: emigration of leukocytes

• neutrophils attracted to area (most abundant WBC)

• attracted to area of injury

  • attach to endothelium and move into surrounding tissues

  • emigration or diapedesis

• eosinphils, NK cells, monocytes

infectious process: phagocytosis

• neutrophils and monocytes enter area of injury

• recognize, engulf, then destroy the organisms

infectious process: exudate

• fluid that leaks out of blood vessels

• cells and debris from phagocytosis

• transport leukocytes + antibodies to area

• dilutes toxins that may be present

• transports nutrients for healing process

types of exudate

• serous

• fibrinous

• purulent

• hemorrhagic

infectious process: systemic symptoms

• if the process does not remain localized

• total body response r/t release of mediators

• stimulation of the hypothalamic fever set point

• pro-inflammatory mediators: interleukins (IL) and tumor necrosis factor (TNF-alpha)

interleukins (IL) and tumor necrosis factor (TNF-alpha)

• fever set point increases, body conserves heat

• defense mech to rid body of organisms, some bacteria less virulent and divide slower

• improves the immune system

• better neutrophil and macrophage function

• improved antibody release and T cell activation

nosocomial infections

infections that occur within a healthcare facility

drug resistant strains in HAIs

• resistance to specific drug

  • MRSA

• resistance to an antimicrobial class

  • CRE

• resistance to multiple drugs/classes (MDRO, MDR)

post-op infections

• resp - atelectasis, increased risk of pneumonia

• surgical wound infections - wound dehiscence, opening of wound - bacteria

• UTIS

how antimicrobial is chosen

• community vs hospital acquired

• site of infection

• suspected organism

always get cultures before starting antimicrobials unless…

suspiciion of meningitis or severe sepsis

minimum inhibitory concentration (MIC)

• grow organisms in tubes that have diff concentrations of an antimicrobial

• min. inhibitory concentration

  • lowest concentration that decreases size of colonies by 99.9% (lowest that kills organism)

trough levels

time between doses, is drug being excreted properly?

peak levels

blood level needs to have enough concentration to be effective

superinfections

• new infection that occurs during treatment for a diff infection

• may be caused by resistant organisms

• antimicrobials also inhibit or kill normal, helpful flora (GIT, skin)

C-diff

• normal intestinal flora are killed by antimicrobial administration

• C-diff can grow w/o control factor

• diarrhea, stool for C.diff toxin, don’t send for culture

• never give antidiarrheal until sure diarrhea not caused by infection

pseudomembranous colitis

• caused by antidiarrheal when diarrhea caused by infection

• life threatening

• dilation of colon

candidiasis

• antimicrobial agents kill normal flora, overgrowth of fungus

• oral and may extend into esophagus, vaginal

• mycostatin, nystatin

antimicrobial resistance

• organisms grow where antimicrobials present

• innate resistance

• mutation from exposure to antimicrobial agent, not give or taken long enough to kill all organisms

beta-lactamase

• enzyme produced by bacteria that cleaves beta lactam ring off antibiotic, making resistant to antibiotics with this ring

• gram + organisms export enzymes into surrounding area

• gram - organisms produce small amts b/t cell wall and cytoplasmic membrane

aztreonam

has beta lactam ring that is not attached to anything else, so not affected by B-lactamase

markers of resistance

• MecA gene

• tested for in lab to identify organisms, esp. MRSA

beta-lactamase inhibitors

• resemble b-lactam structure

• bind to b-lactamase and protect antibiotic from destruction

beta-lactamase inhibitors

• tazobectam: piperacillin - Zosyn

• avibactam: ceftazidime - Avycaz

MDROs ESKAPE

• E Enterococcus faecium

• S Staphylococcus aureus

• K Klebsiella pneumoniae

• A Acinetobacter baumannii

• P Pseudomonas aeruginosa

• E Enterobacter spp

polymixin

• bactericidal for most Gm - aerobic rods

• poor tissue distribution

• substantial toxicity

• systemic use only multi-drug-resistant bacteria

antimicrobials MOAs

• Inhibit cell wall synthesis - bacteriacidal

• Increase cell wall permeability - bactericidal

• Inhibition of protein synthesis - bactericidal or bacteriostatic

• Lethal

• Non-lethal

• Inhibition of DNA/RNA synthesis / alter the function

• Disrupt specific metabolic or biochemical reactions

• Suppress replication of viruses

• Multiple steps

antimicrobials categories

• increase activity against another class of organisms (increase gr - activity for drug og only effective against gr+ organisms)

• improve accessibility

• counteract resistance (B-lactamase)

action against cell wall

• bactericidal

• weaken cell wall

• higher concentration of stuff inside cell

• influx of fluid into cell - burst

  • spills cell contents which causes increased inflammation

• cell lysis and then death

gram + parts

cell wall

gram - parts

outer membrane, cell wall, cytoplasmic membrane

antibiotics that effect the cell wall

• penicillins

• cephalosporins

• carbapenems

• vancomycin

• aztreonam

• teicoplanin

• fosfomycin

penicillin activity and toxicity

• broad activity

• low toxicity - may be anaphylactic allergy

• Mammalian cells do not have a cell wall

penicillin MOA

• works on active infections

• penicillin binding protein

• increase protein synthesis

• increase other cellular processes

• autolysis activation

penicillin category 1: narrow spectrum, penicillinase sensitive

• PCN G - unstable in gastric acid, no oral

• PCN. V - oral, stable in acid

penicillin category 2: narrow spectrum, penicillinase resistant

eathicillin + oxacillin (MRSA), nafcillin, dicloxacillin

penicillin category 3: broad spectrum, amino-penicillins

• ampicillin, amoxicillin

penicillin category 4: extended spectrum- anti-pseudonomal

ticarcillin, piperacillin

where is penicillin metabolized? eliminated?

liver, kidneys

piperacillin-tazobactam

• excreted (mostly unchanged) by kidney

• only given IV

• can disrupt platelet function

  • may see bleeding, but no platelet count change

• gram - organisms

• dose adjusted in renal insufficiency

cephalosporin similarities to penicillin

• bind to PCP

• disrupt cell wall synthesis (bactericidal)

• activate autolysis (bacteria self-destroy)

cephalosporin toxicity

• low tox, but cross-sensitivity to penicillin

• avoid with anaphylactic penicillin reaction

• most common reaction is rash

cephalosporin 1st gen

cephalexin, cefazolin

gram +

cephalosporin 2nd gen

• cefotetan

• cefuroxime + cefoxitin can be given IV, esp. when shortage of IV fluids!!

cephalosprin 3rd gen

• ceftazidime (B. lact. inhibitor)

• ceftriaxone

  • IV push

  • 1st line treatment for bacterial meningitis

  • treatment for gonorrhea infection

cephalosporin 4th gen

• cefepime

• can rapidly penetrate outer membrane

• can be used on gram -

how is cephalosporin absorbed? eliminated?

• poor oral absorption

• most eliminated by kidneys (don’t get peak and trough)

• usually given IV

carbapenems

• very broad coverage

• thought of as last resort

• CROs

• most common is meropenem

imipenem

• 1st one

• combined with cilastin to stop destruction by kidney enzymes

• can induce seizure activity

meropenem

• broad coverage

• no degradation by kidney enzymes

• less seizure activity

vancomycin basics

• own class of med

• commonly used with pt coming in with infection in case of MRSA

• no b. lactam ring

• inhibits cell wall synthesis

• glycopeptide antibiotic

• no oral absorption

vancomycin which type of gram

serious gram + infections

wide distribution

vancomycin elimination and toxicity

• eliminated by kidneys (peak and trough levels)

• toxic - immune-mediated thrombocytopenia (decreased platelet count and increased bleeding risk)

vancomycin infusion-related reaction

• rapid infusion

• flusing, rash, pruritis, urticaria, tachycardia, hypotension

• must infuse slowly, at least greater than 60 min

daptomycin

• cyclic lipopeptide

• disrupt cell membrane

  • bactericidal against gram + bacteria only

  • can be used with MRSA when resistant to vancomycin

• interact with pulmonary surfactant that inhibits antibacterial (can’t use on someone with lung infection)

aztreonam

• monobactam class

• B-lactam ring not fused to another ring (resistant to B-lact.)

• only works on gram - bacteria (resistant to B-lact. producing gram - organisms)

• only IV

aztreonam elimination and adverse effects

• eliminated by kidneys

• thrombophlebitis

• slight risk of cross-allergy to pcn or cephalosporins

intracellular activity drugs

• aminoglycosides

• lincosamides

• macrolides

• oxazolindinones

• streptogramins

• tetracyclines

• glycylcycline

• fluoroquinolones

• cycliclipopeptides

• sulfonamides

• metronidazole

aminoglycosides

• good against gram - bacteria

• staphylococci coverage

• severe reactions: ototoxicity (ears), nephrotoxicity

gentamycin (prototype)

• aminoglycoside

• transported across cell membrane

• requires o2 (aerobic)

• given IV

• concentration 50x higher in kidney than in the serum (and concentrated in inner ear)

• must get into cell to work

• peak and trough levels (with IV dosing)

gentamycin adverse effects

• ototoxicity - balance

• nephrotoxicity - acute tubular necrosis

• neuromuscular blockade - myasthenia gravis - resp. weakness

• confusion, depression, disorientation, numbness, tingling

amikacin, kanamycin, neomycin

• amikacin - broad spectrum, less resistance

• neomycin - topical, highest toxicity (don’t give IV)

tobramycin, streptomycin

• tobramycin

  • better coverage of psuedonomas

  • inhalation - resp. infections, cystic fibrosis

• streptomycin

  • TB treatment

  • plaque

  • tularemia - infection from rabbits

clindamycin

• lincosamides

• -cidal or -static depending on dose

• very toxic

• broad coverage (aerobic g + or anaerobic g+ or g-)

• prophylaxis prior to dental procedures

  • ppl with hip, knee, or valve replacement

clindamycin adverse effects

• risk of C.diff (huge for long-term)

• pseudomembranous colitis

• dryness of skin and conjuctiva

erythromycin

• macrolides

• may be -cidal

• legionnarie’s disease

• mycoplasma pneumoniae

• diptheria

• used to be used for chlamydial infections

erythromycin benefits

• hypomotility

• diabetic gastroparesis

• increase gastric motility and emptying

azithromycin

• long ½ life (daily dosing)

• doesn’t interfere with human protein synthesis (better tolerated)

• absorption

  • capsule - take on empty stomach (decreased with food)

  • suspension - increased with food

linezolid

• oxazolidinones

• specifically developed for MRSA (with resistance to vancomycin)

• oral and PN

• AE: rash, fever, diarrhea, headache, n/v

• oral suspension contains phenylaline - use with caution for: MAOIs, HTN

phenylalanine

• can increase tyramine in the body

• increased level can lead to high BP

• caution with MAOIs - can lead to dangerously high BP

tetracycline

• broad spectrum, major resistance has developed

• used for lyme disease, cholera, rocky mountain spotted fever

• AE: n/v/d, headache, photosensitivity, dizzines, rare anaphylaxis

• concentrate sin bone, liver, tumor, spleen, and esp. teeth

• causes damage to teeth if less than 8 years or all permanent teeth not in place