med microbio--MODULE 7. ANTIMICROBIAL AGENTS

selective toxicity

a pharmacologic effect whose ability to destroy or inhibit the microbe without damaging the human host (desirable outcome when only functional on bacterial cells, not human cells)

*Not all antimicrobic agents do this

theraputic index (TI)

what would a good TI look like and mean

a measure of selective toxicity: ratio of max dose tolerated/min dose required

• The higher the TI the better it is for the patient (high amt tolerated, low amt required to kill bac)

• Every drug has consequence (benefit to risk ratio)

bactericidal and 3 examples

a functional effect capable of killing bacteria, kills microbe as its mech of action

Ex: vancomycin, daptomycin, penicillin

bacteriostatic and 3 examples

 a functional effect capable of inhibiting growth/ reproduction of bacteria (starts when treatment starts) antimicrobic that inhibits multiplication/growth as its mech of action

Ex: clindamycin, tetracyclines, erythromycin, etc

An infection is when there is a presence and inc in numbers of bactera; stop rep means to infection→allows for immune response to function naturally and kill bacteria (helps overloaded immune response when large number of infectious bacteria)

Antibiotic (use in bacteria themselves)

substance produced by a microbe that has the capability to kill/inhibit other microbes; find niche and create agents to elim other competitors

3 sources of antimicrobial agents:

1. Chemical – chemical with antimicrobial action like heavy metals (silver)

2. Synthetic– commercially synthesized and marketed: allows for mass prod of antimicrobic agent, once the structure is known, it can be commercially prepared/synth

   1. ex) insulin (big deal was finding the structure that works so we can mass prod)

3. Microbial– substance produced by a microbe

Antimicrobic spectrum (2 subcategory names)

the variety of microorganisms an antimicrobial agent can effectively inhibit or kill (broad or narrow)

Competitive inhibition

substrate and inhibitor compete for binding to same site on enzyme; halts process

Minimal inhibitory concentration (MIC)

lowest conc of antimicrobial agent capable of preventing growth of the microbe

Minimal bactericidal concentration (MBC)

lowest conc of antimicrobial agent capable of killing the microbe

Serum bactericidal level

and why caused in patient

det. treatment effectiveness in inhibiting/killing the bac isolate responsible for patient infection

*Occasionally used for complications in treatment due to resistance, allergic reactions, etc that limit antimicrobics available for use

susceptible (bacteria)

bacteria that’s growth (whether death or stasis of growth) is impacted by an antimicrobic agent

• a critical aspect of clinical microbio is the determination of antimicrobial susceptibility of bacteria isolated from patients. This is the ultimate goal of what effects an antibiotic treatment will have on the patient (what works in vitro will more than likely work on patient)

Resistant (bacteria)

developed mechanism to resist antimicrobic action

Etest

establish antimicrobic density gradient in agar plate → det. MIC where growth ellipse intersects w scale on Etest strip

Antibiogram:

composite report of antimicrobial susceptibility profiles of bac isolates from w/in a community or locale

combination effect

and example of its implementation (with biofilm)

use more than a single antimicrobic as a treatment strategy, one works but not as fast or potent as needed, so add second; ex) 1 is effective against bacteria that forms biofilm so add 2 to teardown biofilm first that allows 1 to better work

indifference vs additive vs synergy vs antagonism effects of bacteria (w/ visual equations)

• indifference= no additional benefit w combo compared to each one alone (no enhanced eradication. 1x (anti1) + 1x (anti2) = 1x effect. Doesn’t justify combo effect

• additive= effect of one drug adds to effect of second drug; combo justified; 1x + 1x = 2x effect

• synergy= combination produces enhanced effect beyond that of either drug alone; 1x + 1x > 2x effect (more than 2x effect→optimal)

• antagonism= combination effect where one drug counteracts the effect of the other; 1x + 1x < 1x effect; less than 1x effect/drug by itself→ won’t make combo

narrow vs broad spectrum drugs (and example of each)

• Narrow spectrum= effective specifically against one type of organism

  • ex) penicillin is more effective against gram pos than gram neg bac

    • spectrum=gram pos

• Broad spectrum= effective against several types of organism

  • ex) tetracycline is equally effective against gram pos and gram neg

List the 3 groups of organisms that have yielded useful antibiotics.

one example of each

1. Molds:

   1. Penicillin lead field of ID antibiotics and what pattern others began to search for 

      1. Alexander Fleming reported the existence of it in 1928 but was unable to purify for use as an antibiotic. Staphylococcus in region of penicillium colony were undergoing lysis (dying) by some unknown substance produced by the mold

      2. Bacteria were not growing despite food being available; a measurable distance away from the penicillin colony

      3. We copy nature bc microbes inform us how to prevent growth

   2. Cephalosporium is a wheat fungus 

2. Actinomycetes: 

   1. “Branching bacteria”

   2. Streptomyces is a soil actinomycete: og source of streptomycin

3. Bacteria

   1. Bacillus subtilis produces many antibiotics 

Interference with essential metabolites as an antimicrobic mech of action

example (substrate and inhibitor)

antimicrobic disrupts critical metabolic pathway

Enzyme inhibition as an antimetabolic process:

• Reaction w/out inhibitor: S + E → ES → E + P and E starts process again

  • Enzymes speed up reaction to allow for high enough rate for process to allow organism survival, by blocking, reaction does not occur fast enough

• Reaction w/ inhibitor: S + E + I → EI + S (competitive inhibition)

  • Ex: PABA (substrate) and sulfa drugs (sulfonamides inhibitor) compete for binding to the same site on enzymes

Impairment of structural integrity as a antimicrobic mech of action

example

mechanism of action is binding to peptidoglycan thereby disrupting cell wall structure in bac pop that are replicating (primary a mech against gram pos bac)

ex) penicillin which binds to peptidoglycan and disrupts formation of cell wall by making holes

Inhibition of protein synthesis as antimicrobic mech of action

example of drug that binds to 30S reversibly and irreversibly, and 50S reversibly (2)

ribosome disruption/disrupts translation by binding to various points on ribosomal subunit (can be bacteriostatic or bactericidal dep on if reversible or not)

Work by:

1. Bind to 30S ribosomal subunit (reversible–tetracycline)

   1. Irreversibly bind to 30S (aminoglycosides)

2. Bind to 50S ribosomal subunit (reversible–choramphenicol, erythromycin)

Interference of nucleic acid synthesis as an antimicrobic mech of action (3 general ways)

protein synthesis halted and polymerase disrupted

Gen mech:

• Disrupt transcription (DNA→RNA)

• Disrupt replication (DNA →DNA)

• Break DNA molec

Disruption of the cell membrane as antimicrobic mech of action

example (2)

regulation of cell traffic disrupted

Processes: 

• Bind to phospholipids

  • Alter cell perm

  • Disrupt osmotic integrity (req high amt of moisture to survive)

ex) bacitracin, polymixin

what is optimal selective toxicity/TI

no damage of host while ability to destroy bac (TI= max dose tol by host / min dose req to kill)

narrow/broad spectrum of effectiveness, gram pos or gram neg targeted most commonly

narrow is effective against one type, broad is effective against several (gram pos have peptidoglycan in cell wall, gram neg don’t so this is often targeted in gram pos like with penicillin)

Bactericidal versus. Bacteristatic

kill outright or halt growth to allow for immune system to catch up

inhibition of essencial metabolites: drugs (1) and general mech

1. Sulfa drugs

2. Inhibition of critical pathways

impairment of cell wall integrity drugs (6) and general mech

1. Vancomycin, b-lactam drugs, “cillins”, cephalosporins, monobactams, carbapenems

2. Target peptidoglycan

inhibition of protein synthesis drugs (4) and mech

1. Tetracycline, aminoglycosides, chloramphenicol, erythromycin

2. Bind to ribosomal subunits reversibly or irreversibly

interference with nucleic acid synthesis drugs (3) and mech

1. Rifampin, quinolones, metronidazole

2. Prevent transcription/ DNA formation

disruption of cell membrane drugs (2) and mech

1. Bacitracin, polymyxin

2. disrupt/alter cell permeability

sulfa drugs: 

inhibitor name that mimics substrate

general mech

broad or narrow spec

synthetic or natural antimic

selective tox/TI

mech of inhib

adv (2)/disav (3)

PABA (substrate) and sulfa drugs (sulfonamides inhibitor) compete for binding to the same site on enzymes *(inhibition of essential metabolites)

• Folinic acid is the active form of folic acid (all cells need folic acid for growth bc needed for purine and pyrimidine formation)

• Bacteria must synthesize their own folic acid from PABA but mammalian cells do not need to synthesize bc provided in diet (therefore high TI drug if inhibits pathway)

• Sulanilamide (drug) looks structurally similar to PABA and thus compete at first step via competitive inhibition–halkts progression of path that uses purines to make DNA

• Overwhelm env w/ antibiotic to inc winning out competition and elim bac

• Since drug has been used for a long time, now antibiotic resistance

Summary: 

• Synthetic antimicrobial agent

• Broad spectrum (gram pos and neg)

• Selective toxicity (toxic for bac, not for mammalian cells)

• Mechanism of inhib: block bacteria’s ability to produce a metabolite essential for life (DNA)

• TI is high since humans use dietary folic acid and bac have to synth their own (high tolerance by host / low dose needed against bac)

Disadvantages: 

• Bacteriostatic instead of bactericidal (may take longer to red bac numbers since immune sys is needed)

• Insoluble at acid pH (may precipitate in urine if used to treat UTI, which can lead to kidney damage)

• Many resistant strains are present due to widespread use of sulfa drug

Advantages: 

• Readily absorbed into tissues

• Crosses blood brain barrier to treat brain abscesses, which not many drugs do; kept present in hospital formularies 

penicillin: 

general mech

biochem structure of inhibitor

generally selects against ___

broad or narrow spec (variation dep on what)

bactericidal or static

selective tox/TI

mech of inhib

adv (1)/disav (2)

penicillin which binds to peptidoglycan (gram pos have a lot) and disrupts formation of cell wall by making holes (*impairment of cell wall integrity)

A characteristic epitomized by penicillin is presence of a beta-lactam ring in its structure that has anti bacterial properties

• Problem is that some bac have evolved to produce an enzyme beta-lacamase that cleaves the beta lactam ring rendering the antimicrobic ineffective (evolved)

• Ring used in other antimicrobic agents: cephalosporins, monobactams, carbapenems; if can cleave ring, bac will be resistant regardless of type of antimicrobic agent

  • Drug company response to beta-lactamase production by bac has been to make chemical mod to existing structures

• Penicillin G is the initial penicillin

  • Subsequent changes have resulted in many diff types with similar structures (ampicillin, amoxicillin, methicillin, etc)

Other beta lactam antibiotic summary:

• TI: high since effect on mammalian cells is nothing (no peptidoglycan in mammals)

• Activity: disruption of cell wall is bactericidal

• Spectrum: varies and is dependent on R group modifications (tweaking to combat resistance) to antibiotic structure

  • Generally, effects on gram pos>gram neg

• Disadvantages: 

  • Hyper sensitivity reactions– esp penicillin (can elicit all 4 types of hypersensitivity reactions so common)

    • Acts as hapten (bind to make more immunogenic), attaches to albumin, is antigenic, can cause immune probs

  • Microbe resistance

    • Many bac have acquired b-lacamase encoding plasmids that break open b-lactam rings that combat infectious bac

• Advantages: very effective against bac with no b-lactamase

tetracycline:

source

TI

mech

static/cidal

spectrum

disav (3—where rez is mediated from, toxic where, inactivation how)/adv (2)

Source: (where we learned structure from) streptomyces (an actinomycete)

TI: low

• Readily bind serum proteins in stomach that makes it become inactive or minimally active, therefore high doses are needed–this affects min dose req

• Not easily excreted which affects max dose req

Activity: 

• Binds 30S ribosomal subunit in reversible manner (*inhibition of protein synthesis)

• Inhibits rRNA attachment to mRNA codon

• bacteristatic

Spectrum: broad

Disadv: 

• Plasma mediated resistance is common

• Hepatoxic (liver damage) w/ continuous high doses

• Inactivated by foods; pharm rec for take one hr before or 2 hr after meals to prevent binding to food and red absorption

Structure: 4 fused rings with 4 R groups for possible mods

• Bind to small subunit which inhibits rRNA attachment to mRNA codon

• tRNA can’t enter/bind and position self for translation so translation halts

rifampin:

source

mech

static/cidal

spectrum

disav (2)

Activity: bactericidal

Mech: bind RNA pol and prevent transcription (mRNA synth)

• *interference w nucleic acid synth

Source: streptomyces

Spectrum: narrow–gram pos

• Effective against m. tuberculosis 

Disadv: 

• Resistance develops quickly

• Liver toxicity

• Usually used in combination with other drugs

Bacitracin:

source

cidal/static

TI

disav (1)/ adv (1--typical use)

Source: microbial (bacillus)

Activity: bactericidal

Spectrum: limited

• Effective against gram pos (polymyxin is effective against gram neg)

TI: low

• Mammalian cells affected as well as bac 

Disadv: very toxic

Adv: effective and useful as topical ointments for superficial dermatologic infections 

• Triple antibiotic topical ointment with polymyxin, neomycin, bacitacin

Chloramphenicol:

source

mech

static/cidal

spectrum

TI

disadv (2) / adv (1)

Source: streptomyces

Activity: binds to 50S ribosomal subunit in a reversible manner – prevents peptidyl transfer and peptide bond formation

• bacteriostatic

Spectrum: broad

Disadv: 

• Toxic effects at high doses (low TI)

• Interferes with RBC development; can cause aplastic anemia

Adv:

• Readily diffuses into cells and CNS – useful against CSF infection bc can cross blood brain barrier

• Effective against serious brain abscesses

Gentamycin:

example (1/ general naming ends)

mech

static/cidal

source

disacv (3—toxic cond for 2 and ineff against what bac)

aminoglycoside (others all end in -mycin)

Source: streptomyces

Activity: 

• Bind 30S ribosomal subunit in an irreversible manner

• Change shape of 30S, causing misreading mRNA codon (wrong AA added), terminating protein synth

• bactericidal

Disadv: 

• Ototoxic (hearing), nephrotoxic (kidney nephron)

• Ineffective against anaerobic bac

List and describe general mechanisms of bacterial resistance to antimicrobic action.

intrinsic vs aquired resistance

6 pathways to resistance

5 reasons for emergence of antimicrobic resistance

Characteristics of intrinsic (naturally coded and expressed by all or almost all strains of that particular bac species) and acquired resistance (changes in genome through mutation or horizontal gene acquisition that lead to changes in nature of proteins expressed; these changes may lead to alt in structural or functional features of bac, which may result in changes leading to resistance against antibiotics) →common pathways of resistance:

1. Enzymatic degradation or modification of the antimicrobic agent (add or modify enzyme or destroy it)

2.  decrease uptake or accumulation of the antimicrobial agent

3.  altered antimicrobial target (alter step and metabolic pathway so antibiotic doesn't have a place to come and act)

4.  circumvention of the consequences of antimicrobial action

5.  uncoupling of antimicrobial agent–target interactions and subsequent effects on bacterial metabolism 

6.  any combination of the above

Summary and examples:

1. Enzymatic degradation or modification of the antimicrobic agent: Innate production of enzymes that inactivate the drug

2.  decreased uptake or accumulation of antimicrobial agent: Extrusion of the drug by chromosomally encoded active exporters

3.  altered antimicrobial target: lack of affinity of the drug for the bacterial target

4.  circumvent / find way around consequences of antimicrobial action: and accessibility of drug into the bacterial cell

5.  uncouple antimicrobic-target interactions

Thus, antibiotics combat some mech:

*don’t mem, just know this is how antibiotic resistance is combated

Emergence of antimicrobial resistance:

• Mixing of bac gene pool + selective pressure from excessive antimicrobial use and abuse =>survival of the fittest (ones that survive antibiotics)

• Emergence of new genes

•  spread of old genes to new hosts

•  mutations of old genes resulting in more potent resistance

•  emergence of intrinsically resistant opportunistic bacteria 

MIC assessment (microplate method): evaluate and interpret test results/meaning

Lowest concentration of antimicrobial agent capable of preventing growth of the microbe

• tube and microplate methods

•  lowest concentration that gets desired outcome of drug

•  inhibition could be by a bactericidal or bacteriostatic mechanism

• Shows MIC (lowest conc antibiotic that inhib growth) and checks validity of microplate with controls

• Move to next test: (MBC) Streak MIC on agar plates to see if cidal or static mech (if no growth on plate cidal, if growth on plate that is just media then static bc antibi only inhibits growth)

eval and interpret Minimal bactericidal concentration (MBC) assessment

Lowest concentration of antimicrobial agent capable of killing the microbe 

Performed by inoculating agar plates with bac from MIC microwells

• If bacteria do not grow on plates once removed from antibiotic Ridge environment of MIC well, then antimicrobic agent has a kill effect

• If bacteria do grow on plates once removed from antibiotic Rich environment of MIC well, then antimicrobic agent has the effect of growth inhibition 

MIC and MBC use to determine bactericidal versus bacteriostatic effects: (parallel studies)

Bacteriocidal: MIC values are close to or the same as MBC

Bacteriostatic: MIC values are lower than MBC values→easier to prevent growth than kill

• MIC and MBC parallel studies: MIC (lowest conc antibiotic that inhib growth) and checks validity of microplate with controls. Move to next test: (MBC) Streak on agar plates to see if cidal or static mech (if no growth on plate cidal, if growth on plate that is just media then static bc antibi only inhibits growth)

Serum bactericidal test (SBT):

• 2 things needed for test

dilution of serum from patient on antimicrobic regimen (only done on occasion when patient resistant/ allergic/ treatment unfunctional to test if antibiotic is even working) to determine treatment effectiveness in inhibiting/killing the bacterial isolate responsible for the patient’s infection

• Need specific bacterial isolate from isolate (serum from patient)

• Growth of isolated colonies of infectious agent from patient and serum from patient who is on antibiotic (bac + antibi)

Kirby Bauer disk diffusion assay:

Use of paper discs on agar plate that contains growth of bacteria to determine zones of inhibition/bacterial growth 

Etest establishes what, and why might someone chose to do this test over others

Establishment of antimicrobic density gradient in agar plate format – Manual method of providing susceptibility results (MIC) with ease of test performance and costs similar to disk diffusion method 

Describe the principle of disk diffusion and relate it to zones of inhibition

• 4 step method 

• role of national comittee on clinical labroatory services (NCCLS)

• 3 results and their meaning/ how this is determined

(Kirby Baur susceptibility test)

• Method of determining bacterial sensitivity to a panel of antimicrobics

•  used today and tests several at a time

•  results are susceptible, resistant, intermediate

Method:

1. Standardized suspension of bacteria is swabbed over surface of a specific type of agar plate in a manner that results in lawn growth

   1.  we want bacteria all over surface

   2.  three-way streak to prevent isolated colony growth

   3.  known approximate number of bacteria/ density across all assay 

2. Paper discs containing single concentrations of antibacterial agents are placed on inoculated surface

   1.  Filter disk:  saturated with specific concentration of antimicrobial agent

      1. conc=MIC which allows to see which antimic works best

   2. Test multiple antibiotics on same disk

   3. Antibiotic diffuse into  agar in all directions evenly while bacteria is growing during incubation

3.  plates are incubated

4.  diameters and millimeters of zones of inhibition of bacteria growth are measured

   1.  bacteria grow until reach susceptible antibi

 personalized med: specific to particular patient - E coli is from patient sample for example 

National Committee on Clinical Laboratory services:  

• determine when an organism becomes resistant due to changes in concentration of MIC; 

• they constantly monitor and set interpretive standards 

Results: 

• Diameters of zones of inhibition of bacterial growth are measured and recorded as S, R, I

  • S:  sensitive, susceptible: microbial growth is inhibited at concentration safely attainable in the patient

  • R:  resistant: microbial growth is present at concentrations above what is safely attainable in the patient

  • I:  intermediate: microbial growth is present at concentrations above susceptible breakpoint but may be effective under some conditions

Chart to det. S/R/I results

State the principle of the Etest: describe its performance and use: interpret Etest results.

where eclipse intersects scale means what on e test strip

 Manual method of providing susceptibility results (MIC) with ease of test performance and costs similar to disk diffusion method 

Establishment of antimicrobic density gradient in agar plate format 

• Use of thin plastic test strips impregnated on the underside with concentration of gradient of specific antimicro

•  antimicrobic gradient after overnight incubation forms on agar around test strip and gives rise to epileptic area of inhibition

  •  similar mechanism to disc diffusion test with three-way street, except use strips that have different concentrations of diff antibiotics

• MIC is determined as where the growth Eclipse intersects the scale on the e-test strip 

 

State the definition of antibiogram and define its use and importance.

Susceptibility testing importance: 

• Patient has an infectious process and physician needs to know the best choices of antibiotics to prescribe (may already be on antimicrobic if urgent case, this can be tweaked with susceptibility test results)

•  microbial resistance to antimicrobics is suspected–commonly isolated back bacteria tend to develop resistance

•  Epidemiology

  •  Investigate and track spread of infectious agents through a population

  •  antimicrobic resistance patterns can be a supportive identifying characteristic

•  testing new drugs

  •  efficacy assessment of new drug is necessary to be put on market 

• Test types: disk diffusion (Kirby Baur), Etest, automated methods (microplate susceptibility results (MIC) obtained by use of special instrumentation and reagents, but costly; VITEK 2 system incubates and reads cards w/ diff biochem and antimicrobes which is suspended in microbe in question)

Antibiograms:

• Monthly report in hospitals of every major organism

• Composite report of antimicrobial susceptibility profiles of bac isolates from w/in a community or locale

• Some bac have typical antibiograms 

  • E. coli sensitivity patterns (resistant to some endemic in a location) 

• Trends of resistance in specific pops/locations are ID

• Best assess first line of treatment when sensitivity results are not yet available

• Track emerging resistance in the hospital/community

define MRSA.

origin

cephlasporin role (what gen it took to find antimic activity

2 types

resistance is due to what

localized infection meaning

“Methicillin-resistant S. aureus”

Cephalosporins and MRSA:

• Took 5 generations to find beta-lactam antimicrobic w MRSA and VRSA activity (ceftaroline)

• Last antibiotic in line bc possible side effects, but powerful

• Only drug that works on MRSA so valuable

Origin:

• Used to be thought of as health care associated MRSA, but now community associated CA-MRSA(skin, soft tissue, etc) → why gyms have desanitizing sprays

• MDR=multi drug resistant (many drugs are in this cat)

• 10% s. Aureus isolates in US are susceptible to penicillin

  • Many strains while resistant to penicillin remains susceptible to penicillinase stable penicillin, such as oxacillin and methicillin 

• Strains that are resistant to Amoxicillin and methicillin are termed methicillin-resistant staph. Aureus (MRSA)

  • Now some are resistant to all beta-lactam agents, including cephalosporins and carbapenems

Types:

HA-MRSA= Isolates often are multiply resistant to other commonly used antimicrobic agents,

•  erythromycin, clindamycin, tetracycline

•  nosocomial infections of patients or visitors

CA-MRSA=Isolates are often resistant only to beta-lactin antimicrobics and erythromycin

•  since 1996, MRSA strains resistant to Vancomycin have been reported

  •  not used as first line drug unless patient has resistance to organism due to low TI

Resistance: 

• Chromosomally mediated resistance via mechA gene

Localized infections: 

• Superficial

• Inflammatory response is elicited; immune response 

Describe the importance of MRSA.

• why commonly transmitted

• resistant to what antimic agents

• Some people Harbor staph A in nasal cavity as part of normal flora, but can transmit to others (passive carrier)

• Now some are resistant to all beta-lactam agents, including cephalosporins and carbapenems

Define VRE, describe its importance and identify major problems associated with it.

• causitive agent

• endocartitis vs UTI infections and bac

  • cidal or static needed

  • type of therapy needed (3, and 4th if none work)

"vancomycin-resistant enterococci"

Enterococcus bacteria:

• Prefix means intestinal tract

• Common pathogen of the urinary tract

• UTIs are usually treatable with ampicillin or penicillin

• Most common UTI causing gram pos bac (most common in general is E. coli, which is gram neg)

Causative agent of endocarditis (heart)

• Requires bacteriocidal antimicrobic therapy

• Synergistic effect (combo antimic treatment) of combo therapy is treatment of choice

  • Ampicillin or penicillin (vancomycin for penicillin-alergic patients)

  • Aminoglycosides such as gentamicin (usually resistant to aminoglucosides when they are administered alone)

Vancomycin-resistance in enterococcal endocarditis can be life threatening:

• Problematic

• Enterococci are highly resistant to antimicrobics thereby causing vancomycin to be the only treatment option

  • If the enterococcus is VRE, then resistance to vancomycin is present and no antimicrobics remain that are therapeutically effective for treatment

Generations of cephalosporins/ what is special about this family of beta-lacams/cidal or static/mech

1–against gram pos

2–against both gram pos and neg

3–greatly against gram neg, enhanced against b-lacamase producing gram pos

4–true broad spec

5–MRSA and VRSA beta lactam antimic

Largest and most diverse family

Bactericidal

Mimic structure of D-ala link in peptidoglycan and bind to active site of penicillin binding proteins 

only treatment for MRSA and VRSA

treatment for TB patients

gen 5 cephalosporin—>some rez to this now too

rifampin

two drugs that cross bbb

sulfa drugs and chloramphenicol

ESBL bac tend to be gram pos or neg

neg