Pharm Block 4-2

• G which is given O or P(mostly P) and Pen V which is oral only
• Give Pen G every 4 hours for sever infections like meningiococcimea
• Procaine and benzathine penicillin G are repository forms with longer half lives

• E. coli(80%), Proteus mirabilis, Salmonella, Shigella, H influenzae, H.pylori(almost 100%)
• Strep pneumo,
• Listeria monocytogenes(100%) only sensitive to ampicillin can cause neonatal menenditis and puperal endometritis
• Moraxella catarrhalis
• Enterococci
• Borellia bergdorfi

• Nafcillin, oxacillin, Cloxacillin, Dicloxacillin
• Used for methicillin sensitive staph aureus and staph epidermitis
• Nafcillin no good for enterococcus or e coli

• Narrow spectrum penicillins
• GAS- Strep pyo
• strep pneumo- 95% of bact pneumonia
• Some gram positives
• Treponema pallidum
• No good for Staph aureus Bacteroides Fragillis or ecoli

• beta lactamase that destroy the antibacterial actions ( staph resistance to penicillin G)
• Mutation of the penicillin binding targets of penicillins ( staph resistance to methicillin)
• Alter porins to decrease penetration

• Cidal
• Interfere with cell wall synthesis by binding penicillin binding proteins located in the bacterial cytoplasmic membrane.
• inhibit transpeptidases that crosslink proteoglycan chains
• Also activate autolytic enzyes that cause cell wall lesions
• Best for acute infections

• variable oral absorption
• Minimally metabolized and excreted in urine (blocked by probenecid)
• Ampicillin partly and nafcillin mostly are excreted into biliary tract
• Penicillin only has minimal access to CNS, eye, or prostate.

• Ampicillin P/O
• Amoxicillin O
• Ticarcillin P
• Piperacillin P

• Methicillin P
• oxacillin P
• Naficillin P
• Cloxacillin O
• Dicloxacillin O

• A first generation Cephalosporin administered Parenternally with a T1/2 of 1.8 hrs
• Strep/Staph- 4+ sensitive
• H flu- 1+
• Gram Negatives- 2+

• It is an extended range Penicillin, can be used to treat: Ecoli and mirabilis 3+ sensitivity
• Pseudomonas, Enterobacter, Indole + orgs, and Proteus are 4+ sensitive
• Bacteroides Fragilis is 3+ sensitive

• An extended range Penicillin Organisms that are sensitive to Ticarillin are- Ecoli and proteus Mirabilis 2+
• Pseudomonas, Enterobacter, and Indole+ proteus 2+
• Bacteroides Fragilis 2+

• An extended range penicillin.
• Only Ecoli and Proteus Mirabilis are sensitive 2+

• Treatment of Step Pharyngitis
• Prophylaxis against Rheumatic fever
• Syphilis treatment

Some staph organisms are resistant to normal penicillins, need to use penicillinase resistant drug.

• Otitis Media
• Sinusitis
• Pneumonia
• UTI
• Lyme disease
• Can only use these drugs if sensitve strains of a given organism are causing the disease.

Gram negative organisms especially Pseudomonas infections. Also Mixed intra abdominal infections if caused by strains sensitive to these drugs.

Often replaced now with tazobactam (piper+beta lactamase inhibitor)

• Diarrhea is common due to disruption of normal intestinal flora ( often with Amocicillin and augmentin)
• Seizures possible with high doses of penicillin
• Allergic hypersensitivity- anaphylactic rxns (rash and urticaria) 1 in 10,000 doses

• Elevated hepatic transaminases
• Drug fever
• Nephritis- usually methicillin related
• Penias, hemolytic anemia (coombs positive)

• RAST blood test for screening
• then follow up skin tests for major and minor determinants
• life/health threatening rxns are rare

• First generation cephalosporins both given orally
• Cephalexin has a t1/2 of .8 hrs
• Cefadroxil has a t1/2 of 1.3 hours

• A second generation Cephalosporin given Parenternally
• Mostly gram positive action, some gram neg
• Non MRSA staph and strep are 4+ sensitive
• H flu is 3+ sensitive, Gram Negatives are 3+ sensitive

• Second generation cephalosporins that can treat both administered parenternally
• Non MRSA staph and strep 2+
• H. Flu 2+
• Gram Negative 3+
• Bacteroides 3+

• second generation cephalosporins, all administered orally
• Cefprozil is the best for gram negative coverage out of the second gens

Surgical Prophylaxis and soft tissue infections

Treatment of Intra abdominal infections

• third generation cephalosporins given parenternally. Can be used to treat- non MRSA staph and strep 3+
• H. Flu 4+
• Gram negatives 4+
• bacteroides 1+
• Ceftriaxone is the drug of choice for Borellia Bergdorfi

• A third generation cephalosporin given parenternally. Can be used to treat non MRSA staph and strep 1+
• H. Flu 4+
• Gram Negatives 4+
• Pseudomonas 4+
• Bacteroides 1+

• 4th generation cephalosporin given parenternally can be used to treat Non MRSA staph or strep 3+
• H. Flu 4+
• Gram Negatives 4+
• Pseudomonas 4+
• Bacteroides 2+

Third

Cefoperazone and Ceftriaxone

Cefotaxime is metabolized in liver

Enterococci, Listeria, and MRSA

First

• Variable oral absorption
• Renal elimination
• Cefoperazone and Ceftriaxone are well excreted into the biliary tract
• Cefotaxime is metabolized in the liver
• Only cephalosporins that enter CNS effectively are Third gen (ceftriaxone)

Cefoxitin and Cefotetan

• Ceftriaxone and Cefotaxime given for serious pediatric infections like meningitis, broad spectrum but no good for anaerobes, pseudomonas, enterococci, listeria and MRSA
• Ceftriaxone used in gram neg liver abscess
• Ceftazidime given for pseudomonas infections
• Cefepime has a very broad spectrum but no good on anaerobes, Enterococci, Listeria, or MRSA

• Rash/ urticaria
• not much cross allergy between penicillin and cephalosporin
• Disulfiram-like reaction – cefamandole or cefoperazone (ingestion with alcohol
• produced headache, nausea, vomiting, abdominal pain)

• Bleeding diathesis- cefamandole (no longer avail in US) or cefoperazone
• Phlebitis at infusion site
• Biliary ubstruction when rapidly infused-ceftriazone

• Amoxicillin+ clavulanic acid(beta lactamase inhibitor)
• administered orally
• Drug of choice for animal bites

Ticarcillin+ Clavulanic acid- ad ministered parenternally

Ampicillin + Sublactam ( beta lactamase inhibitors) given parenternally

• Piperacillin+ Tazobactam (beta lactamase inhibitor)
• given parenternally

• A beta lactamase inhibitor that is isolated from Streptomyces Clavuligerus.
• Irreversibly binds beta lactamase

• to broaden the spectrum of effectiveness against
• Staph Aureus, H. Flu, Bacteroides, Moraxella Catarrhalis, and Gram negative enteric bacteria.

Increases the MIC

• a monobactam beta lactam that is administered Parenternally and does not penetate the CNS
• used to treat gram negatives including pseudomonas, not effective on anaerobes.

• A carbapenem beta lactam administered parenternally with no CNS action.
• Administered with cilastatin to inhibit renal inactivation by dehydropeptidase1
• Rarely causes neurologic rxns like seizures- usually assoc with high dose/renal failure

A carbapenem beta lactam

A carbapenem beta lactam

No but some organisms make extended spectrum beta lactamases that can inactivate carbapenems.

• As a last resort for resistant organisms, have a very broad spectrum.
• NOT used for listeria, MRSA, some enterococcus strains, some pseudomonas, and some anaerobes.
• can be used as empiric treatment of patients that "crash" secondary to suspected resistant organism
• also used for mixed infections

• A complex Gluco-polypeptide, unrelated to
• other antibiotics
• excreted renally, not well absorbed orally, and has inadequate CNS/Eye/Prostate penetration

• Irreversibly inhibits
• biosynthesis of peptidoglycan polymers in cell wall of
• dividing gram positive organisms

Blocks cell wall synthesis

Has a narrow spectrum works on resistant gram positive orgainsms including MRSA, enterococci and pneumococci

Clostridium Difficile also susceptible

Vancomycin

• not as good for lung infections
• Drug of second choice for Pseudomembranous colitis caused by clostridium difficile (because of the concern about Vanco resistance, Metranidazole

• Renal toxicity
• Auditory toxicity
• Red man syndrome- fixed with slow infusion

A lipopeptide antibiotic given Intravenously

• Bactericidal by disrupting multiple aspects of the bacterial plasma membrane function ,
• including peptidoglycan synthesis, lipoteichoic acid synthesis, and
• bacterial membrane potential.

• Narrow, works on gram positive organisms including linazolide resistant MRSA, vancomycin resistant enterococcus (VRE)
• Usually has a low MIC

• Skin and soft tissue
• infections #
• Sepsis #
• Endocarditis #
• # (With resistant gram positive infections)

NOT yet approved for children

• Rapid concentration dependent activity
• concentration dependent post antibiotic effect.
• given once daily
• excreted via kidney

• Transientmuscle weakness, myalgias after 6 - 11 days of Rx. CPK levels (MM isoenzyme) rose 2-3 days before and
• peaked at 10,000-20,000 U/L. CPK normal
• in 1 week

• Once daily dosing (4 mg/kg) may increase the
• therapeutic –toxicity ratio by increasing efficacy and decreasing skeletal muscle adverse effects associated with twice daily dosing

• Aminoglycosides
• Tetracyclines
• Tigecycline
• Chloramphenicol
• Macrolides/Ketolides
• Clindamycin
• Synercid
• Linezolid

• kanamycin P/O, Neomycin O/Topical, Streptomycin P
• Tobramycin P, Netilmicin P, AmikacinP, and Gentamycin P/T

• Binds to 30 S subunit of Bacterial Ribosome
• Bacteriocidal Inhibitors of Protein Synthesis
• Blocks formation of initiation complex
• Causes misreading of mRNA template - cidal
• Inhibits translocation
• Prevents polysome formation
• Blocks subunit association

• Polar compounds so not orally absorbed
• Excreted renally- dose adjustment in renal insufficiency
• Poor CNS/Sputum/Bile/ Prostate penetration
• pH dependent activity 7.4 best

• Demonstrateconcentration dependent killing – high levels of antibiotic facilitate entry through cell wall and membrane
• Demonstrate post-antibiotic effect
• Therefore, administer one or two larger doses each day to achieve high peak levels
• Toxicity is related to trough levels and host tissue “recovery time”

• Inactivating enzymes called group transferases- confered by plasmids
• Inhibition of drug penetration into the organism
• Decrease affinity of the 30s subunit target for the antimicrobial

E coli, Proteus, Klebsiella, Enterobacter, Serratia, Pseudomonas, and moderate gram positive coverage.

• often used in combo with cell wall active drugs like beta lactams
• used in serious gram negative infections of hospitalized patients
• Empiric treatment of neonatal infections
• Second line of drugs for mycobacterial infections

• Significant renal toxicity – acute tubular necrosis, reversible and dose related
• Ototoxicity- auditory and vestibular damage could be irreversible- dose related
• Not to be used in pregnancy
• Neuromuscular blockade

• Tetracycline
• Oxytertacycline
• Doxytetracycline
• Minocycline

• Variable oral absorbtion- impaired by food
• Moderate tissue distribution
• Enterohepatic cycling
• Tetracycline excreted in the urine, doxycycline in feces
• Antagonistic when used in combo with beta lactams

facillitate efflux of the drug from the bacteria or decrease the entry of the drug

• Bacteriostatic bind reversibly to the 30s subunit of bacterial ribosome
• Inhibits attachment of aminoacyl tRNA

• Gram positive Staph and strep
• Gram negative enterics
• Anaerobes
• Atypically- Mycoplasma, Chlamydia, Chancroid, Rickettsia, Borrelia, Entamoeba

Variable efficacy on top 3

• Treatment of subacute bronchitis secondary to H flu and strep pneumonia
• Atypical pneumonia
• STDs; Prostatitis (doxycycline)
• Rocky Mountain Spotted Fever
• Lyme disease
• Acne

• GI- Nausea, abdominal pain, diarrhea
• Fetal and child effects on bones/teeth- CONTRAINDICATION
• Hepatic Necrosis (especially with doxycycline)
• Renal tubular acidosis
• Photosensitivity
• Headache, vestibular (dose dependent), Pseudotumor Cerebri
• Jarisch Herxheimer rxn

• A derivative of minocycline only given via IV
• Binds 30s ribosomal subunit with high affinity blocking tRNA binding
• Bacteriostatic, good tissue distro, post antibiotic effect, metabolized in liver and excreted into billiary tract.

• MRSA, MRSE, VRE, resistant pneumococci and enterococci
• Acinetobacter and other gram negative aerobes and anaerobes, some mycobacteria, and mycoplasma, NOT pseudomonas
• Synergistic with Rifampin
• Skin and skin structure infections
• Intra-abdominal infections
• Not approved for children (See tetracyclines

• Cross hypersensitivity to tetracyclines
• Nausea and vommiting
• Headache and pseudo tumor cerebri
• Possible bone and tooth discoloration
• Transaminase elevation

• Antibiotic that is rarely used due to feared toxicity
• Has excellent oral absorption but can be administered IV
• Best distribution b/c lipophillic
• Metabolized in the liver by glucuronyl transferase
• Inhibits cytochrome P450

Binds the 50s subunit of the bacterial ribosome and inhibits peptidyl transferase activity.

Bacteriostatic

• Antibiotic inactivating enzyme production- conferred by plasmid
• Reduction of permeability to drug.

• Broad but no good for staph or pseudomonas
• Works for H. flu, Neisseria meningitides, salmonela, anaerobes, and rickettsia

last drug used for brain abscess, typhoid fever, and rocky mountain spotted fever.

last due to toxicity

• 1/40,000 irreversible aplastic anemia
• dose related aplastic anemia
• Gray baby syndrome- inability to conjugate chloramphenicol because of decreased levels/immature glucuronyltransferase

• Erythromycin
• Clarithromycin
• Azitromycin
• Telithromycin

• Used orally mostly but IV available
• Poor CNS and Eye penetration
• Concentrates in Respiratory secretions
• Azitromycin is concentrated in phagocytic cells and other tissues
• Mostly hepatic metabolism and excretion, some urinary excretion

• Bind 50s subunit of bacterial ribosome preventing ribosomal translocation.
• Bacteriostatic for the most part.

• high level of resistance by alteration of the receptor on the ribosome (plasmid mediated) Strep pneumo is one
• Production of inactivating enzymes
• Increase efflux mediated by mef A (low level resistance
• Decrease in permeability to the drug

• Penicillin V- 15%
• Erythyomycin- 35%
• Augmentin- 8%
• Cefpodoxime-20%
• Azithromycin- 35%

• Sensitive gram + but not entero coccus
• some anaerobes
• Salmonella (typhoid fever-azithromycin)
• Legionnaire's disease
• Mycoplasma
• Chlamydia
• Bordetella Pertussis (azithromycin)
• Campylobacter
• Atypical Mycobacteria (claritromycin)

• Substitute for penicillin in respiratory bacterial infections
• Atypical pneumonia; whooping cough
• MAI (clarithromycin)
• Resistant Salmonella (Azithromycin)
• Contra indicated in pregnancy (except azithromycin)

• Abdominal pain and nausea
• Cholestatic hepatitis (erythromycin estolate)
• Associated with higher incidence of pyloric stenosis if used in infants
• Multiple drug interactions secondary to inhibiion of hepatic cytochromes (not azitryomycin)

Metabolized in the liver by CYP 450 and CYP 349

used on penicillin resistant pneumococci, H. Flu, Moraxella Catarrhalis, B pertussis, mycoplasma, legionella, and chlamydia

• Blurred vision
• Gi disturbance
• Prolonged QT interval
• Exacerbation of myasthenia gravis
• Multiple drug interactions

• A Lincosamide antibiotic
• bacteriostatic
• Similar to macrolides and as such there is some cross resistance.
• good oral absorption and tissue penetration but no CNS or Eye
• Resistance usually mediated by increased efflux

• Good for Gram positives including Staph aureus and severe invasive strep. Not for enterococci
• Good for anaerobes
• High incidence of pseudomembranous colitis secondary to C difficile overgrowth

• A Streptogramin Combination
• quinupristin 30% and Dalfopristin 70%
• Metabolized and excreted by liver
• Only given IV
• Binds 50s subunits prevents ribosomal translocation- bacteriocidal

Staph aureus and epidermidis, Strep pyo and aglaci, some enterococci

Causes drug interactions, phlebitis (most common), Jaundice, arthralgia and myalgia

• An oxazolidione
• absorbed well orally 100%- not altered by food
• metabolized by liver but excreted by kidney
• Better penetration into lung than vancomycin (significant for pneumonia)
• has low serum protein binding independent of drug concentration

• Binds the 50s subunit and inhibits initiation complex and translocation of tRNA
• Bacteriostatic
• Resistance from decreased affinity of target for the drug

• All aerobic gram positives, especially resistant staph strep and enterococci
• Toxicity causes thrombocytopenia, neutropenia, reversible marrow suppression
• Also a weak MAO inhibitor