1. Confirm the presence of infection

2. Identify the pathogen

3. Select presumptive therapy-host factors and drug factors

4. Therapeutic steps

1. fever

2. WBC (left shift)

3. ESR, CRP

4. Pain, inflammation

5. disease specific signs

WBC count as high as 30,000-40,000

Presence of immature bands is and indication of inc. bone marrow response to infection

Bands >10% is indicative of bacterial infection

Other tests-

Non-specific signs of inflammation

non specific

ESR - how far RBC fall in one hour

CRP- (C-reactive protein)

0.5-1.0 normal

Stains

Serologies

Culture and Sensitivity

Features of Gram (+)

1. Purple stain

2. Thick cell wall

3. high peptinoglycan

Lower peptinoglycan

Thinner Cell wall

Stain Pink

1. Used for empiric anBX tx, routinely on:

-CSF for meningitis

-Urethra smears for STDs

-Abscesses for effusions

-Respiratoru tracts infections

+good specimen <10 epithelial cells per LPF, PMN's present

1. Most definitive method for the diagnosis and inventual tx of infection

2. Required appropriate collection and transportation to the laboratory

3. Avoid contamination with normal flora

4. (bactec) for rapid detection

-detection and quantification of antibodies directed against specific pathogen or its components

teqniques:

-Immunoflorescemce: Varicella, syphilis, lymes

-Latex agglutination:  meningitis, L pneumophelia

-ELISA enzyme linked immunoassay: HIV, herpes, RSv, ginorrhea, H. Pylori, pneumococcus

1. Hybridization DNA probes

2. nucleic Acid Amplification methods

-PCR polymerase chain rxn

Selection of therapy:

Host Factors:

Drug allergies

age

pregnancy

renal and hepatic funx

site of infection

concomitant drug therapy

Underlying disease statis

Antimicrobial activity

spectrum of activity

pharmacokinetics

pharmacodynamics

tissue penetration

advere effect profile

cost and convenience

Bacteria growth:

Target of antibiotics:

1. Need cell wall

2. Need to split/divide

3.need proteins with division

1. Narrow-less expensive, low resistance

2. Extended

3. broad-dont know where or what infection

MIC is the lowesty antimicrobial concentration that prevents visible growth of an organism after 24 hours of incubation

++the measure of how sensitive or resistant an organism is to the antibiotic tested

Microbial sensitivity:

Susceptibility testing method:

1. Macrodilution method

2. Microdilution method

3. kirby-bauer disk diffusion

4. E-test

5. Automated methods

Susceptibilty testing

automated methods

-rapid Susceptibilty systems often incorporate the use of microprocessors, robotics, and microcomputers

-the vitek system: growth measured by photometric assessment of turbidity every 4 hour for 15 hours

-The microscan system: Uses fluorogenic substrate hydorlysis as an idicator of bacterial growth

1. Susceptible

2. Intermediate

3. Resistant

-based on relationship between MIC and peak serum concentration of the abx at typical doses

-Peak should be 2-4 x MIC to be susceptible

-Overuse of abx

-Low dose- inadequate doses

-prolonged exposure

-inappropriate abx

-day care

-Penetrate cell

-reach target

-kill  organism

-Decreased permeability

-Drug efflux

-drug inactivation

-altered target

Penicillin-binding proteins

PBPs facilitate cell-wall formation for bacterial cells (cell growth)

binds to PBP and prevents adequate cell-wall formation. growth is inhibited

-antibiotics cannot bind to altered PBPs and cannot inhibit cell-wall formation. Growth continues.

Concentration-dependent killing rate:

(CDKR)

More bacteria are killed at higher concentration of antibiotic

-some aminoglycosides and flurpquinolones exhibit CDKR

- Penicillins and other B-lactam abx usually do not exhibit CDKR

Persistent effect of an antibiotic on bacterial growth after the antibiotic is removed from bacterial culture

-most bactercidal abx exhibit a PAE against susceptible pathogens

-clinical application-allow for less frequent dosing

Concentration dependent goal: AUC24/MIC 25 minimum; 100 ideal

AUC24= 24 hour area under the curve

Quinolones

Aminoglycosides

azithromycin

Concentration

Independent Goal:

Above MIC for >40% of the dosing interval

Penicillin

Cephalosporins

Erythromycin

Clarithromycin

1. Empiric therapy

-likely pathogens for the site of infection

-pt hx

-local susceptibility

2. refine therapy based on culture and sensitivity results

3. Monitor therapuetic response and adjust therapy as needed

Staph

Step

Enterococcus- most difficult to kill

H. Flu

Neisseria

Moraxella catarrhalis

in GI tract

EKP: E. coli, Klebsiella, Proteus

ESP: Enterobacter, Serratia, providencia

1. Gram +

2. Gram - cocci & cocco-bacilli

3. Enterobacteriacea

4. Pseudomonas aeruginosa

5. Anaerobes

S. pneumoniae

H. flu

M. catarrhalis

S. pneumoniae

N. meningitidis

H. Flu

S. pneumoniae

H. Flu

M. Catarrhalis

Fungus?

S. pneumoniae

H. flu

M. catarrhalis

S. pneumoniae

Mycoplasma

H. flu

Pseudomonas

Staph

E. coli

Klebsiella

proteus

Ent

E.coli

Klebsiella

Enterococcus

pseudomonas

Staph

1. Confirm the presence of infection

2. determine site of infection

3. identify pathogen

4. Select presumptive therapy

-likely pathogen, host factors, drug factors

5. Refine therapy- based on C&S results

6. Monitor therapeutic response

Staph aureus

Staph empidermis

S. pneumoniae

Group A (B-hemolytic Step): S. pyogenes

Group B Step: S. agalactiae

Group D:

1. Enterococcal sp; E faecalis, E.faecium. E. durans

2.non-enterococcal sp: S.bovis; S.equinus

Strep Viradans Group

peptococcus

peptostreptococcus

Clostridium

Diphtheroids

Haemophilus influenza

brodetella pertussis

Neisseria

Moraxella catarrhalis

1.Enterobacteriae

-E.coli;Klebsiella sp, proteus, enterobacter sp, serratia sp, providencia sp

2.Pseudomonas

3.Anaerobic

-Bacteroide fragillis, bacteroides sp, fusobacterium sp

Anearobic bacteria

(gram +)

peptococcus

peptostreptococcus

clostridium sp

Anaerobic bacteria

gram (-)

bacteroides fragilis

bacteroides sp

fusobacterium so

prevotella sp

polyphyromonas

Staph

where?

1. Rickettsia

2. treponema pallidum

1. Rocky mountain spotted fever

2. Syphilis

1. EKP:

2. ESP:

1. many; uti; gi

2. gi