This class of drugs are used to treat gram positive organisms (except enterococci, MRSA), anaerobes (except clostroidium dificile), and some protozoa like toxoplasma and plasmodium

Lincosamides - Clindamycin

This class of drugs is used to treat mycoplasma, legionella, chylamydophilia, campylobacter jejuni, bordatella pertussis

Macrolides - Erythromycin, clarithromycin, azithromycin

Clarithromycin/Azithromycin - can treat H. Influenzae, M. Avium, and Toxoplasma Gondii.

Does not treat strep pneumoniae.

How are neomycin/kanamycin administered?

Topically 

These drugs interfere with the binding of the 30S portion of ribosomes in bacteria 

Tetracycline

Aminoglycosides (rapid tight binding to 30S - streptomycin, or 50/30s - neomycin/kanamycin, gentamycin/tobramycin/amikacin 

How is amikacin administered? 

Systemically 

This drug is used to treat mycobacterium marinum and nocardia 

Minocycline 

Best method of absorption - lincosamides

Oral - good 

This class of drug inhibits DNA gyrase in bacteria 

Quniolones - Cipro/levo/moxi/gati/trovafloxacin

What type of administration should you give for macrolides? 

NO IM!

Give erythromycin orally (33% absorption - will get theraputic concentrations), as well as azithro and clarithromycin.

Azithromycin may be administered IV 

How are tetracyclines absorbed? 

Incomplete but adequate from small intestine/stomach

-impaired by divalent cations 

What drug will milk interfere with, or magnesium? 

Tetracyclines 

Do quniolones have good bioavailability 

Yes! Cipro - 70% others, 80-90% 

How are lincosamides metabolized?

10% unchanged in urine

less than 10% unchanged in feces

Only reduce dose if hepatic and renal failure 

Should you adjust dose of lincosamide in a person with renal failure? 

No only hepatic and renal failure 

How are macrolides metabolized? 

5-15% are unchanged in urine/feces

Don't need to decrease dose in people with renal dysfunction 

How are quinolones metabolized? 

Lots of metabolization (good for treating UTI)

60% excreted in urine unmetabolized

10% in feces unmetabolized

30% metabolized in feces 

How are tetracyclines excreted? 

Tetracyclines - good renal excretions

Doxycycline - both renal and feces excretion 

What is a good drug to treat UTI's? 

Quinolones 

Distribution of lincosamides 

Everywhere except CNS 

Distribution of Macrolides

Everywhere except CNS

Erythromycin - crosses placenta

Azithromycin gets high tissue levels 

Which macrolide gets high tissue levels? 

Azithromycin 

Which macrolide crosses the placenta? 

Erythromycin 

Where do tetracyclines distribute? 

Good distribution in all tissues/body fluids, even CNS (25% serum but not best for meningitis) 

Where do quniolones distribute to? 

Everywhere except CNS 

How are lincosamides metabolized? 

Hepatic 

What macrolide is a slow metabolizer, only requiring one dose per day?

Azithromycin 

What is the main drug that promotes cloistridium dificile overgrowth? 

Lincosamides (clindamycin) 

Which drugs may cause GI cramps, irritability, cholestatic hepatitis at high doses, and reversible partial deafness? 

Macrolides (erythromycin, clarithromycin, azithromycin) 

Ketolides have tighter binding to ribosomes than macrolides.  To what organism does this increase its activity to?

Strep pneumonia 

What is a potential fatal consequence of ketolides distinguishing it from macrolides?

Liver toxicity 

This results in a mild or reversible rash, photosensitization, vaginal candidiasis and diarrhea 

Tetracyclines 

This drug stains teeth in children 

Tetracyclines

This drug leads to fatty hepatic necrosis in pregnant women in high doses 

tetracycline 

Adverse effects of demeclocycline 

Nephrogenic diabetes insipidus when high dose used.  May be used to treat SIADH 

Glycyclines (tigecycline, glycycline and monocyclines) can be used to treat what? 

MRSA, more gram positive activity than tetracyclines, less activity versus proteus and providencia, no activity versus pseudomonas 

These have been known to cause damage to cartilage (ruptured achilles tendons) as well as nausea, headache, and vomiting, as well as QT interval prolongation 

Quinolones 

This quinolone has been known to cause acute hepatic failure 

Trovafloxacin 

 1st generation cephalosporins have activity against what organisms?  

Gram positive staph, strep.  Commonly acquired gram negatives like E. Coli, Klebsiella, Proteus

Names of drugs in 1st generation class: 

Cephalexin, Cephradine, Cefadipixil (oral), Cefazolin (IV) 

Names of 2nd generation cephs: 

Cefactor, Cefuoxime, Cefoxitum, Cefotetan 

Spectrum of activity of 2nd generation cephalosporins     

Less activity versus gram positive, more gram negative activity

Cefoxitin/Cefotetan - enteric anaerobes (Bacteroides, Prevotella)

Cefuroxime/Cefactor - H influenzae, N meningitidus 

Names of 3rd generation cephalosporins 

Ceftrilaxone (oral), cefotaxime, Ceftazidime, Cefixime, Cefopodoxime 

Name of 4th generation cephalosporin 

Cefepime 

3rd generation cephalosporin activity 

More activity versus nosocomial gram negative bacilli (enterobacer, Citrobacter, Serratia, Neisseria)

Ceftazidime - activity versus pseudomonas but less versus gram positive cocci

4th generation cephalosporin activity 

Broad activity against streptococci, MSS, gram negative bacilli like pseudomonas aeruginosa 

Are any cephalosporins active against MRSA/enterococci/Listeria? 

No 

Bind to PBP's and interfere with cell wall construction

Cephalosporins, Carbapenems, Monobactams 

Absorption of cephalosporins 

Oral or IV but not both

Cefuroxime can be administered both ways 

How are cephalosporins excreted? 

Through active glomerular secretion/organic ion transport.  Blocked by probenecid.

Doses need to be decreased in severe renal disease 

Distribution of cephalosporins 

All get adequate tissue concentrations

3rd/4th generations get into cSF

Ceftriaxone - increased biliary concentration 

These drugs cause a delayed hypersensitivity reaction/anaphylaxis 

Penicillins, cephalosporins 

This class of drugs cause Gi bleeds by inhibiting post translational carboxylation of glutamic acid residues in vitamin K dependent clotting factors 

Cephalosporins - Cefotetane, cefoperazone 

This class of drugs has activity versus gram positive strep/staph (except for MRSA)/and enterococci (except for E. Faecium and ampicillin resistant E. faecalis) as well as most gram negative rods 

Carbapenems (Imipenem, meropenem, ertapenem) 

Ertapenem is ineffective versus psuedomonas and enterococci 

Do carbapenems have good activity versus enterococcus? 

No, does not tx MRSA either 

How are carbapenems administered? 

MUST BE GIVEN IV. 

How are carbapenems excreted? 

They have the same renal transporter as penicillins, and cephalosporins 

Where are carbapenems distributed? 

All body tissues except urine for imipenem (combine with cilistatin) 

This class of drugs causes an increase risk for seizures

Carbapenems 

This antibiotic is highly active versus gram negative bacilli and is drug of choice 

Monobactams (aztreonam) - no effect on gram positive cocci, and anaerobes 

How are monobactams administered? 

IV 

How are monobactams excreted? 

Exclusively by glomerular filtration/kidney excretion 

This does not cross react with penicillin in producing a hypersensitivity reaction 

Monobactams 

This is a topical treatment for aerobic gram negative bacilli 

Neomycin, kanamycin 

This group of drugs treats aerobic gram negative bacilli including pseudomonas and are synergistic versus enterococci 

Aminoglycosides 

This is used for decontamination of the GI tract before surgery 

Kanamycin 

This drug treats hepatic encephalopathy or can be used to prevent wound infection when used toppically 

Neomycin 

These drugs result in progressive non oliguric renal insufficiency 4-5 days after administration with proximal absorption affected most. 

Aminoglycosides 

These drugs result in irreversible damage to the organ of corti and crista ampullaris as well as neuromuscular blockade

Aminoglycosides 

This is related to aminoglycosides and binds to 30S subunit of gram negative bacilli and cocci.

It is occasionally used to treat N. Gonorrhea and urethritis 

Spectinomycin 

This is used to treat most gram positive cocci except MRSA/Enteroocci, and enteric gram negative cocci (except pseudomonas, actineobacter), as well as anaerobic bacteria and Rickettsia 

Chloramphenicol 

Administration of chloramphenicol 

Oral>IM do not use IM

Can chloramphenicol be used to treat UTI's? small amounts are unmetabolized in urine 

YES 

This drug can be used to treat meningitis because of its hydrophilic/lipophilic portions 

Chloramphenicol 

This drug may cause bone marow aplasia or reversible dose dependent neutropenia, as well as gray baby syndrome 

Chloramphenicol 

Treats MRSA and other gram positive cocci, as well as E. Faecium and faecalis including vancomycin resistant strains 

Oxazolidinones (Linezolid) 

Has 100% bioavailability because of size and hydro/lipophilicity 

Oxazolidinones 

(Oxazolinidone) Linezolid distribution 

Ok levels in skin, lungs, CSF is 70% of serum 

How are oxalidinones (linezolid) metabolized? 

50% metabolized in urine

30% unmetabolized in urine

10% metabolized in feces

10% unmetabolized in feces

10% unrecovered 

This drug causes GI disturbances like nausea and diarrhea.  Thrombocytopenia if over two weeks, reversible, MAO inhibition (avoid adrenergic/serotonin drugs/tyramine foods) 

Linezolid 

All gram positive cocci except for E. faecalis (ok for fecium) 

Streptogramins 

Dalfopristin - interferes with peptide synthesis by binding to 50S subunit

increases binding for qunipristin

Quinipristin - binds tightly to 50S subunit preventing further polypeptide formation (synergistic). 

Streptogramins 

How are streptogramins absorbed?

Negligible because such a large molecule must give IV 

Distribution of streptogramins 

Adequate into bile, skin, WBC, poor CSF 

Metabolites of quinipristin 

Antibactericidal, conjugated to glutathione. 

Inhibits p450 enzmes, increasing levels of other meds

Streptogramins (Synercid) 

This class of drugs causes arthralgias and myalgias including an increased sensitivity to pain.

Venous phlebitis occurs in 50-75% of patients in small veins so central catheters must be put in. 

Streptogramins

This class of drugs targets gram positive cocci

Lipopeptides 

Which drug has a lipid that binds to bacterial membrane leading to efflux of K+? 

Lipopeptides 

How are lipopeptides administered? 

Lg molecule so use IV 

Where in the body do lipopeptides distribute to?

Ok skin, soft tissue, urine, decrease in bronchial fluid 

How are lipopeptides excreted?

80% unchanged renal excretion

5% fecal recovery 

Causes reversible myopathy

Lipopeptides 

Has PABA ring (in sunscreens absorbs UV) 

Sulfonimides 

This class of drugs is used to treat strep (except pneumonia), and also used for H. influenzae, H. Ducreyi, E. Coli, Brucella, Vibrio Cholera, Yersinia, Chlamydia trachomatis, nocardia 

Sulfonamides 

What is the mechanism of sulfonamides?

PABA and tetrahydropteric acid -> dihydrofolic acid - folic acid donates and receives 1 C groups

PABA-- folic catalyzed by tetrahydropteric acid synthetase which is inhib by sulfonamides

We can get folate from other sources, bacteria cannot 

Where do sulfonamides distribute in body? 

Good concentration in tissues, peritoneum, pleura, synovia, and CSF 

How are sulfonamides metabolized?

Metabolized in liver and excreted (acetylation/clucoronidation) 

This drug has higher solubility in urine that is alkalinized 

Sulfonamides 

Causes rashes/hypersensitivity, that cease when meds are stopped.  Also causes tubular deposits, acidic urine, as well as hemolytic anemia. 

Sulfonamides 

Are sulfonamides ok in pregnant women and babies?

No - Metabolic pathways haven't developed in babies, and may get kernicterus 

This drug is used to treat anaerobic bacteroides, prevotella

Clostridium, fusobacteria, trichomonas vaginalis, giardia, entamoeba histolytica 

Nitroimidazoles (metronidazole) 

This drug works by causing a reduction of a nitro group that causes toxic products to be released leading to bacterial cell death 

 Nitroimidazoles

Metronidazole 

Distribution/Absorption of metronidazole 

100% after oral dose, IV similar, goes to nearly all tissues including CSF pleura, liver, saliva, vagina 

How common is resistance to metronidazole? 

Rare because low uptake into bacterial cells 

Do you need to adjust doses of metronidazole in renal failure? 

NO!  Metabolism is solely in liver 

How is metronidazole excreted from the body? 

60-80% in urine 

Causes mild sx but sometimes nausea, vomiting, anorexia, disulfiram reaction in drinkers 

Metronidazole 

How are penicillins administered? 

IM/IV

Oral penicillin - Penicillin V is stable in stomach 

This drug is used for outpatient treatment of UTI/bronchitis/sinusitis from gram negative bacteria 

Ampicillin (often used with aminoglycosides - gentamycin for more gram negative coverage)

These drugs are used for treating pseudomonas

Anti-pseudomonal penicillins - Ticarcillin/Timentin/Piperacillin/Zosyn/Carbenicillin/Mezlocillin 

This drug is used as first line defense against MRSA 

Vancomycin

This drug is used against (methicillin resistant) staph epidermidis 

Vancomycin 

Enterococci are acutely sensitive to this drug 

Ampicillin 

This drug can be used to treat hospital acquired gram negative aerobic bacteria including pseudomonas aeruginosa 

Monobactam - Aztreonam