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A. Penam

B. Penem

C. Carbepenem - no sulfur

D. Cefem

E. Monobactam

F. Penicillianic acid

G. 6-Aminopenicillianic acid

___ is without the sulfur molecule and. All other beta lactams have sulfur in their structure.

____is the only beta lactam with a 6-member ring.

__ and ___ are the core structure of the modern penicillin.

A - amide group

B - cis hydrogen

C - thiazolidine ring

D - carboxylic acid group

E  - Beta-lactam ring

F- bicyclic structure

Penicillin is degraded by beta lactamase into ____

penilloaldehyde

Both are IM only

difference: Benzathine is added to stabilize Pen G against BLases to maintain serum drug levels (reduce excretion), while Procaine is added to reduce pain at injection site.

1. Oxacillin - IV

2. Nafcillin - IV

3. Methicillin - IV

4. Dicloxacillin - oral (best)

5. Cloxacillin - oral (weak)

1. Pen VK

2.  Dicloxacillin & Cloxacillin

3. Aminopenicillins - Ampicillin & Amoxicillin

4. Augmentin

1. Carboxypenicillins- Ticarcillin & carbenicillin (activity against G- and pseudomonas)

2. Piperacillin

1. Clavulanic acid

2. sulbactam

3. tazobactam

Amoxicillin- Clavulanate (Augment) - oral (the only one)

Ampicillin-sulbactam (UNasyn) - IV

Piperacillin-taxobactam (Zosyn) - IV

Ticarcillin-Clavulanate (Timentin) - IV

___ was the first cephalosporin and was made from a fungus from sewer water. 

 the key molecule in penicillin is ____.

They have 2 R groups -

R1 = modify spectrum of activity

R2 = change in PK & ADME

 N-methylthiotetrazole (MTT) side chainà alcohol intolerance and prothrombin deficiency.

All 3^rd gen have ____ that increase activity against gram (-)s.

Cilastatin inhibits ____and prevents Imipenem degradation.

Vancocin - IV and oral for colon infection (C.diff)

Vibativ - IV only

All parenteral

Nebulizer: Tobramycin (nebulizer for cystic fibrosis

Opthalmic: Tobramycin and Gentamicin

Topical:  Neomycins (ointment and for prophylaxis for bowel surgery) 

tetracycline + acid = anhydrotetracycline (nephrotoxic)

tetracycline + basic = lactone ring (inactive)

Do not recommend tetracycline to children under ___yrs old.

B-lactam

glycopeptide

aminoglycoside

macrolide

tetracyclines

Quinolones

Sulfomethoxazole/Trimethoprim

Oxazolidinone

Chloramphenicol

Oral and parenteral

ophthalamic - Moxifloxacin and levofloxacin

Tetracyclines

fluoroquinolones

Ceftriaxone

1:5 (trim-to-sulfa) - trimethoprim is 100x more potent

MOA of sulfomethoxazole- inhibits dihydropteroate synthase and then trimethoprime (inhibit dihydrofolate reductase)

Microbiome is the totality of all the microbes in your gut (not in blood) and on your skin and their interaction with their environment.

___microbial typing is used to identify bacterial species

 classification of people based on their gut microbiota….not dependent on diet or ethnicity (not an accepted concept)

Parasitesàuni- or multicellular that need host to survive.

Fungi –> uni- or multicellular organisms ex. Mold or yeast

Protozoa à single-celled organisms that require a host to survive.

Viruses à non-living, noncellular organism that require a host to grow.

Bacteria à living, single cell organism

Coccià spherical à seen in clusters, chains, pairs and tetrads

Bacilli à rod shaped à see in thin or broad filaments

Spirochetes à helical

Pleomorphic à various sizes and shapes

1. G+ have a thick peptidglycan layer but no outer membrane, while G- have a lipopolysaccharide/phospholipid outer membrane but thin peptidoglycan layer.

2. G+ have teichoic and lipoteichoic acid, while G- have periplasm and periplasmic space

3. G+ stain purple, while G- stain pink

___ of lipopolysaccharide is used for serological-typing of strains

Primary stain àCrystal violet

Mordant à Iodine

Decolorizerà Alcohol

Counter stain àSafarin

1. Has G+ cell wall structure

2. Has glycolipids and mycolic acid

3. Stains best with acid-fast stains

Mycoplasma

Mycobacterium

Rickettsia

Legionella

Bruscella

Fransicella

Chlamydia

Carbolfuchsin stains 

Fluorescent stain

Sexual reproduction in Bacteria occurs when uptake of ___

exogenous DNA 

-

1. They produce slime that reduces the penetration of drug into the biofilm to reach the bacteria.

2. The slime reduces nutrients to some bacteria, putting them in stationary phase, making them hard to target.

3. Biofilm increases adaptation mechanism of the bacteria.

4. They also have pumps that pump out drug, reducing concentration.

colon > mouth > genitals and armpit > intestine > head hair >stomach > skin > eye > lungs 

Outer ear

Skin

Urethra

Which are normally sterile sites as far as we know:

Jejunum

Stomach

Respiratory tract

Large intestine

Eyes

Duodenum

anaerobes lack important enzyme needed for detoxifying pathway against oxygen radicals, while aerobes have this enzyme.

Phase 1: brief exposure to oxygen

Anaerobes that live outside of animals & humans, but prefer soil, sediments of fresh and sea water.

Ex. Clostridium is found in soil as endospores

Anaerobes are most likely to be found in all except:

A. Oral cavity

B. GI tract

C. peritoneal cavity

D. Genitourinary tract

C. 

Remember: Heavily colonized mucosal surfaces  can be portals of entry into tissues, blood stream, & usually sterile body sites

Anaerobes are common seen in these infections:

Why culture for microbiota?

How long does it take to manually:

a) grow a culture?

b) biochemically ID each colony?

c) Get sensitivity testing for each colony?

a) 24 hrs 

b) 24 hrs (6hrs if by machine)

c) 24 hrs (6hrs if by machine)

MIC – minimum inhibitory concentration

Which of the two is a qualitative method:

Kirby-bauer (disk diffusion method)

or 

Dilution test method

Kirby-bauer (disk diffusion method) - qualitiative (mm) --> does not measure MIC

Dilution test method - quantitative

35 degrees celcius temperature

Ambient air

for 16-18 hours

measure zone of inhibition

False.

Faster replication (virulent)= smaller zone of inhibition

Slower replication (not virulent) = larger zone of inhibiton

1. In KB, the bigger/wider the diffusion the more sensitivity the bug is to the drug; in MIC, the smaller the growth in the broth the more sensitive the bug is. [Inversely related]
2. KB is qualitative, while MIC method is quantitative

define Minimal bactericidal concentration

 (MBC)

is lowest concentration of antibiotic that kills 99.9% of bacteria.

MBC is also a quantitative test like MIC

E test: quantitative test that measures antimicrobial density gradiant in a Kirby-Bauer agar plate. Agar is IMPregnated with antimicrobial concentration gradient

Which is used against fastidious organisms and anaerobes :

MIC 

MBC

E-test

1. Pen V 

2. Dicloxacillin 

3. Cloxacillin

4. Ampicilli

5. AMoxicillin

 N-acetylglucosamine and N-Acetylmuramic acid (abbreviated NAG and NAM)

Note: Hanging down from the N-Acetylmuramic acid (NAM) is a 5 amino acid peptide à the bottom one is clipped off leaving only 4. the last is a D-alanin. So you have a repetition of D-alanine-D-alanine peptide.

Porins = outer membrane

Pumps = inner membrane

Kidney elimination;

except for antistaph/penicillinase-resistant penicillins

aka Extended-spectrum Penicillins:

carbenicillin, ticarcillin, mezlocillin and piperacillin

True cephs: good aerobic G+ acitive, some G-

cephamycins: best for anaerobic G-

strong aerobic G- and moderate aerobic G+ activity

Ceftriaxone & Cefotaxime for streptococcus (s. pneumo)

Ceftazidine for pseudomonas

Ceftizoxime for anaerobes

3 Unique Properties of Ceftriaxone (Rocephin):

Chelates with calcium IV.

3

cephalosporins that can penetrate CNS

Cefotriaxone (Rocephin)

Cefotaxime (Claforan)

Cefepime (Maxipime)

CephalosporinsMay Prove Sub-Efficacious 

1. hypersensitivity

2. Nephrotoxicity

3. Diarrhea/ GI upset

Drugs with MTT (1-methyl-5-thiotetrazole) like the cephamycins, cause alcohol intolerance and descreased prothrombin ( increase prothrombin time in coag)

ADR: are mostly due to CNS

Glycopeptide prevents polymerization (remember, beta lactams prevents transpeptidation or crosslinking via inhibition of glycopeptidetranspeptidase

Redman syndrome - IV vancomycin

Ototoxicity and nephrotoxicity

QT prolongation: Telavancin > vancomycin

Parenteral

Nebulizers - tobramycin

Topical - neomycin

Ophthalamic - gentamicin

1. low oxygen (anerobes are resistant)

2. low pH

3. high Ca2+

4. high Mg2+

5. High osmolarity

1. Nephrotoxicity

2. Ototoxicity

3. Neuromuscular paralysis

Hypersensitivity (rare)

Doxycycline 

Minocycline

1. Heptatic and renal toxicity

2. GI discomfort - diarrhea/vomitting due to C. diff overgrowth

3. Photosensitivity

4. Teeth discolorization

Outdated TC - Fanconi syndrome - nephrotoxic --> N/V, polyuria

Best for G+ and ok for some G-, good for atypicals

Azithromycin is opposite: best for G- and weak against G+

Oral

Azithromycin is oral and IV

Erythro - Hepatic

Clarithro - Renal and Hepatic

Azithro - Hepatic as bile

1. Metallic taste

2. Ototoxicity

3. Cholestatic jaundice

4. QT prolongation

G+ and community-acquired G- respiratory pathogens, and atypicals

False: cross-resistance only with lincosamide due to having the same MOA/binding site

Remember: telithromycin binds at two sites on thr 50S and has no cross-resistance with macrolides, even though it is derived from erythromycin and share a similar structure.

CLINDAMYCIN is oral or IV

Clindamycin palmitate is a prodrug for oral 

phosphate ester form is given parenterally

1. Diarrhea

2,. Pseudomembranous colitis - overgrowth of C. diff

3. Local thrombophlebitis (IV admin)

4. Skin rashes

Dalfopristin (streptogramin A): Quinuprisitin (streptogramin B) 

in a 70: 30 ratio

Brand name is SYnercid

Dalfopristins (Streptogramin A) binds to the 50S and causes a positive allosteric effect that increases the binding affinity of quinupristin (streptogramin B)

Quinupristin (streptogramin B) binds to the 50S and inhibit peptide chain elongation and causes chain termination.

1. bone marrow suppression (anemia/leuokopenia/thrombocytopenia)

2. Aplastic anemia

3. Gray Baby syndrome

4. Tissues with high O2 demand

Gray Baby syndrome and Tissues with high O2 demand are ADRs of 

1. Myelosuppression (same as chloramphenicol)

2. Pseudomembranous colitis (same as clindamycin)

3. Peripheral or optic neuropathy

4. Serotonin syndrome

Tyramine rxn - avoid food/drink with tyramine

Neurotoxicity

Nephrotoxicity

Bronchospasm - if colistin is inhaled

Quinolones prevents the resealing of DNA breaks – DNA replication and transcription are affected. Affects most G+.

Strong against G- and some G+, pseudomonas (Cipro, Levo, Oflox), and enterobacter, and atypicals.

Levo, MOxi, Gemi for respiratory strep, 

Moxi for anaerobic G+ and G-

Piperacillin

Ciprofloxacin

Rifampin

Fluoroquinolones

Remember: avoid cholesterol-binders from tetracycline

Photosensitivity

Tendonitis

QT prolongation

CYP450 inhibition

Hemolytic anemia

Acute pneumonitis

Interstitial pulmonary fibrosis

Do not give in elderly due to risk of renal dysfunction and pulmonary ADR.

1. Neurotoxicity

2. Disulfiram-like effect (as seen in cephamycins due to MTT)

3. Carcinogenic & Teratogenic

4. Steven-Johnson syndrome

1) polymyalgia (pain in several muscle groups)

  2) pseudojaundice (skin discoloration due to blood constituents, not true hepatic disease)

  3) anterior uveitis (inflammation of the uvea; the second or vascular coat of the eye,

Decreases folic acid synthesis by inhibiting the enzyme dihydropteroate synthase, which incorporate para-aminobenzoic acid (PABA) into dihydropteroic acid, a folic acid precursor.

No folate = no cell division

Which sulfonamides are used for:

1. treatment of burns

2. opthalmic infections

3. leprosy

4. cleanse GI 

1. Silver sulfadiazine

2. sulfacetamide

3. Dapsone

4. Sulfasalazine

Hemolytic anemia

Anorexia, nausea and vomiting

Hypersensitivity - rashes

Agranulocytosis or aplastic anemia

Crystalluria

Steven-Johnson

 organisms that co-exist with the host and may even be beneficial

Colonization is achieved when an organism is established on a body surface and it requires attachment to host cell and reproducing.

Invasion requires penetration of physiologic barriers and other host defenses

b.      Intracellular organisms must also penetrate into cells

Spread occurs via direct extension through tissues or along tissue planes, through the vasculature and lymphatic systems, and through other mechanisms 

Normal flora secrete ____ that inhibit growth of

other organisms

Cell-mediated ex. T lymplocytes and antigen-presenting cells (dendritic cells)

Humoral ex antibodies and complement system

1. Defensive - attachment/adherence, recognition, proliferation

2. Offensive - dissemination/spreading, toxins, tissue damage

3. Multifunctional - both offensive and defensive

4. Robustness of the organism

5. multidimensional - works under certain conditions ex. beta lactamase

exotoxins have to be INJECTED to causes symptoms of infection ex. tetanus, botulinum, diptheria, anthrax

Endotoxins have to be RELEASE to cause symptoms of infection ex. lipopolysaccharide