Interested in a specific antibiotic? Control-find to learn about it. 28 pages of unique antibiotic facts!

1. Natural Penicillins (Pen VK, Pen G, Pen G
Procaine/Benzathine/Procaine & Benzathine)
Penicillin VK and Penicillin G
 Pen G: Unstable in gastric juice (pH 2), thereby limiting absorption (IV only)
 Pen VK: More stable, higher serum concentrations
 Short T1/2, Renal elimination (tubular secretion)
 Removed by hemodialysis
 Bactericidal compounds. Maximal activity is based on TIME ABOVE MIC
o Concentrations must be above MIC for 50% of the time for maximal
effectiveness (30% for stasis).
 Spectrum
o Oral anaerobes (but not gut anaerobes like bacteroides/fusobacter)
o Gram positives
 Strep & Strep pneumoniae
 Viridans strep
 E. Faecalis, but not faecium
 Neisseria.
 Treponema pallidum (Syphilis)
 DO NOT cover MSSA/MRSA
 Indications
o Primarily syphilis
o Others:
 Endocarditis
 Meningitis
 Strep pharyngitis
 Streptococcal toxic shock
Penicillin G Procaine (Long acting parenteral)
 IM
 Absorbed over about 2-4hrs
 Challenges associated with this drug:
o Requires daily administration
o Neisseria were resistant

2.  May cause dizziness
Penicillin G Benzathine (Long acting parenteral)
 IM
 Drug remained in serum for up to 4 weeks!
 Challenge: severe joint pain
Penicillin G Benzathine/procaine (Long acting parenteral)
 IM
 LESS painful than benzathine
Antistaphylococcal Penicillins (Oxacillin, Nafcillin,
Dicloxacillin)
Oxacillin & Nafcillin
 Spectrum:
o Gram positives
 Strep & S. pneumo
 Viridans strep
 MSSA but not MRSA
 IV ONLY – gastric acid causes breakdown
 Short T1/2
 Hepatic & Biliary excretion
 Distribute into multiple tissues (skin/joint/lung/urine/CSF [with inflammation]), bile,
peritoneal cavities
 May cause increased transaminases – more likely in these two drugs because their
elimination is hepatic
Dicloxacillin
 ORAL!
o Increased F compared to oxacillin and nafcillin

3.  Still have a short half-life
 Used for mild SSIs
 Again, covers MSSA but not MRSA
Extended-spectrum Penicillins
 Aminopenicillins (Ampicillin, Amoxicillin, Amp/Sulbactam, Amox/Clav)
 Ureidopenicillins (piperacillin/tazobactam)
Ampicillin
 Has enhanced cell wall penetrating capability due to being a zwitterion at neutral pH.
This allows them to easily penetrate through a gram negative cell’s porins.
 Absorption is SATURABLE. Increasing dose does not produce greater effect. Higher
doses lead to more diarrhea (this drug’s main problem).
 Penetrates lung, bone, CNS.
 Used empirically in Listeria infections (esp. CNS)
Amoxicillin
 Oral ONLY
 Reduced diarrheavs.ampicillin
 Primaryuse isfor upperrespiratorytractinfections
o UsedempiricallyagainstS.pneumo (highdose)
Ampicillin/Sulbactam
 IV only(2 ampicillins:1sulbactam)
 Minimized impact of beta-lactamases, penicillinases, and cephalosporinases.
 Sulbactam is a “suicide inhibitor”
o Permanently inactivates beta-lactamases. Cannot be reused.
 Sulbactamhas weakactivityagainstNeisseriaandAcinetobacter
 Both have shortT1/2, renal elimination.
 SulbactampenetratesCSF,lung,andbone similartoAmpicillin.
 Empiricuses:
o Surgical prophylaxisforintra-abdominal surgery
o Headand neckinfections involvingthe oral cavity
o Sinusinfections
o MDR Acinetobacterinfections
 Definitive uses:
o Intra-abdominal,headandneckinfections,and gynecologicinfections

4. Amoxicillin/Clavulanate
 Only available in ORAL formulations
 Suicide inhibitor
 Inhibits beta-lactamases
 In contrast so sulbactam, no activity against Acinetobacter
 While amoxicillin is renally eliminated, clavulanate is eliminated by renal & hepatic
mechanisms.
 Primary complaint is diarrhea.
 Primary use is in upper respiratory infections:
o Sinusitis
o CAP
o Otitis media
o Strep throat
Penicillin/tazobactam
 IV only
 Short T1/2, renal elimination
 Extensive distribution into bile, CNS, lung, skin, urine, bone, peritoneum
 The only thing it does not cover is MRSA
 More likely to cause cholestatic jaundice than other beta-lactams
 Uses:
o Healthcare infections where MDR is suspected
o Intra-abdominal infections
o Pneumonia
o Complicated skin/skin structure infections
o Fever/neutropenia
Cephalosporins
 1st : Cefazolin, Cephalexin, Cefadroxil
Cefazolin & Cephalexin & Cefadroxil

5. o Cefazolin: IV ONLY! The only 1st gen with poor F
o Cefazolin has unique use in surgical prophylaxis
o Short T1/2, renal elimination
o CSF penetration = POOR. Can’t be used for CSF infections. Active efflux from
BBB.
o Good penetration into skin, bone/joint, urine, and lung (variable)
o 1st gens do not cover strep pneumo.
o Uses:
 SSIs; MSSA; S. pyo/Agalactiae
 UTIs; E. Coli
 Definitive therapy for MSSA (cefazolin)
 2nd: Cefprozil, cefaclor, cefuroxime, Cefotetan, Cefoxitin
Cefprozil, Cefaclor, Cefuroxime, Cefotetan, Cefoxitin
 Bioavailability: Good for all except Cefotetan and Cefoxitin
o These are both IV ONLY
o Cefotetan has the longest half-life
o Both of these agents have anaerobic activity and are used as intra-abdominal
agents
 All are renally eliminated
o Cefprozil has the lowestrenal elimination
 Still struggle with CSF penetration
 2nd gens can be broken down into respiratory and cephamycins
o Respiratory:
 Cefprozil
 Cefaclor
 Cefuroxime
o Cephamycins (just rememberthat they’re theIV forms)
 Cefoxitin
 Cefotetan
 They cover the same things except cephamycins cover anaerobes.
 Respiratory cephalosporin uses:
o Upper/lower respiratory infection
o Otitis media
o UTI
 Cephamycin uses:
o Intra-abdominal infection
o Mycobacterial infection (cefoxitin)

6. o Surgical prophylaxis
 Cefotetan may cause a disulfiram-like reaction
 3rd: Cefixime, cefdinir, cefpodoxime, ceftriaxone, cefotaxime
Cefixime, cefdinir, cefpodoxime, ceftriaxone, cefotaxime
 Cefixime:Usedforgonorrheamanagement
 CeftriaxoneandCefixime: Longest3rd
genhalf-lives
o  Once dailydosing
 All have prettylowrenal clearance so itis lesslikelytohave toadjustfor renal dysfunction
(biliaryclearedaswell)
 What we’ve beenwaitingfor.. CSFpenetration!
 NO activityagainstESBLand POORactivityagainstAmpC
 Unlike 2nd
gens,theylose activityagainstgutanaerobeslike bacteroides
 NOT ideal forMSSA – firstand secondgensare BETTER
 Uses:
o CNSinfections
o Upper/lowerresptractinfection
o Otitismedia
o UTIs
o Bone/joint
o SSIs
o Intra-abdominal infections
 More frequent CNSside effects due totheirCSFpenetrationabilities
o Seizures
o Confusion
o Delirium
 More frequentdiarrheabecause 3rd
gensare the onlycephalosporinswithbiliary elimination
 Ceftriaxoneiscontraindicatedinneonates<28 days (hyperbilirubinemia)
o Ceftriaxonebindswithcalcium,formingRinger’slactate solution
o Biliarysludgingandnephrolithiasismayoccur.
 Cefdinirshouldbe takenseparate fromironsupplements 2hoursbefore orafterdose.

7. Antipseudomonal and Antistaphylococcal Cephalosporins
 Antipseudomonal: Ceftazidime,Cefepime, Ceftazidime/avibactam, Ceftazolane/tazobactam
 Anti-staphylococcal (anti-MRSA): Ceftaroline
Ceftazidime
 Activity against Achromobacter and stenotrophomonas, which is not seen with other
members of the 3rd gen family
 UNSTABLE against ESBL and AmpC
 Ceftazidime should not be used for gram-positive infections.
 Covers every gram-negative except Acinetobacter. Because of its instability against
AmpC/ESBLs, it is not ideal against species like Enterobacter/Citrobacter/Serratia.
 Poor activity against B. fragilis
 Can penetrate CSF with inflammation
Cefepime
 POOR activity against Achromobacter and stenotrophomonas.
 STABLE against AmpC
 Better gram-positive coverage (up to MSSA); PREFERRED for gram (+) over ceftazidime
 Some activity against Acinetobacter
Ceftazidime/Avibactam
 Avibactamallowsforinhibitionof ESBL,AmpC,KPCand OxaA
o Avibactamisa non-suicidal inhibitorandcanbe recycled.
 As withceftazidime,still notidealforgrampositives.
 Much bettercoverage againstESBL producingbacteria(Enterobacter, Citrobacter,Serratia,P.
aeruginosa) thanceftazidime alone
o Althoughitdoeshave activityagainstESBL/AmpC,itsactivityis notbetterthan
carbapenems
 Predominantuse in KPC-producingorganisms
Ceftolozane/tazobactam
 Similartootheranti-pseudomonalcephalosporinsBUTithas greateractivityagainst
Pseudomonasaeruginosa.
o It isactive againstcarbapenem-resistance pseudomonas.
 Use forP. aeruginosainfections(especiallyforcarbapenem-resistantisolates)!

8. Ceftaroline
 Ceftarolineisthe active metabolite. Ceftaroline fosamil isthe prodrugthatgetsconvertedto
active ceftaroline byphosphatases.
 ACTIVEagainstMRSA (anti-staph/anti-MRSA agent)
 NO activityagainstESBLand poor activityagainstAmpC
o Losesactivitypseudomonas/acinetobacterandreducedactivityagainst
Citro/Entero/Serratia
 Usedin pneumonia,bacteremia,SSIs
 ADEs
o CNS:seizures,confusion,delirium
o GI: N/V/D
o Renal:interstitial nephritis
o Anaphylaxis:CROSSREACTIVITYwithPCN allergy.DONOTUSE in patientswith
immediate onsetreactions(anaphylaxis)
o Hematologic:neutropenia,anemia,thrombocytopenia, FalsepositiveCoombstest
Carbapenems (Imipenem/Cilsatin, Meropenem,
Doripenem, Ertapenem)
Anti-pseudomonal carbapenems:Imipenem/Cilastatin,
Meropenem, Doripenem
 Cilastatin used with imipenem to inhibit DHP1, an enzyme that degrades imipenem
 MeropenemandDoripenem have amethyl groupthatblocksDHP1 hydrolysisandcanbe used
withoutcilastatin.
 MeropenemandDoripenemhave reducedepileptogenic potential (seizures)
 CSF penetration!(greatestinmeropenem)
 Of the beta-lactams,theyrequire the shortestamountof time above the MICtowork
effectively.
 These drugscovereverythingexceptMRSA,E.faecium, andStenotrophomonas.Thatiswhy
they’re nicknamed“Gorillacillin.”
 Theyare all stable againstESBLsand AmpC
o Because of this,theyhave a tendencytoselectforresistantbacteriaand are usually
reserved asa lastline of defense whenotheranti-pseudomonal drugslikeCefepime or
Pip/tazofail orthere isclinical worseningwhile takingthese medications.

9.  Potencyinorder:Doripenem>meropenem>imipenem
 All carbapenems(inc.ertapenem) interactwithvalproicacidandprobenecid.
Ertapenem
 Thisdrug DOES NOT COVER:
o Pseudomonas
o Acinetobacter
o E. faecalis
o E. faecium
 Why??
 Its structure has anioniccharacterthat resultsindecreasedpenetration
throughthe porinsof gram-negativebacteria.
 What’sits use then?
o It standsout because of itshalf-life.Itrequiresonly once daily dosing.
 Easestransitiontohome care
 Like the othercarbapenems,isitisstable againstESBL and AmpCand inactive againstS.
maltophilia.
Monobactams (Aztreonam)
Aztreonam
 ONLY active in gram-negative bacteria.
o Not active in Neisseria or Acinetobacter
 While the same MOA as other beta-lactams (binding PBPs), it has a specific high affinity
to PBP-3. PBP-3 is a septum peptidoglycan transpeptidase used in cell division.
o Bactericidal; time dependent killing; T>MIC of at least 50% required
 Short half-life, renal elimination
 Administered IV, IM or Inhaled
 POOR eye penetration and POOR CSF penetration without inflammation
 Requires renal adjustment
 ACTIVE against Metallo-beta-lactamases (S. maltophilia) but INACTIVE against ESBLs and
AmpC
o Main mechanism of resistance to aztreoname is hydrolysis by beta-lactamases
 CAN BE USED in patients with penicillin allergy
 Can also be used in combination with another beta-lactam when an aminoglycoside or
fluoroquinolone is not appropriate.

10. Aminoglycosides (Neomycin, Kantamycin, Gentamicin,
Tobramycin, Plazomicin)
Neomycin, Kantamycin, Gentamicin, Tobramycin
 AG’s are NUCLEOPHILIC molecules that can easily be inactivated by transferring their
own electrons – makes them an easy target for modification enzymes
 Unique membrane penetration
o AG’s must pass through the outer membrane and the cytoplasmic membrane.
 To get through the outer membrane, AG’s create porins that induce their
uptake with Mg (II) bridges.
 They then diffuse through the periplasmic space where they encounter
the cytoplasmic membrane
 They get through the cytoplasmic membrane via energy-
dependent phase I (requires electron transport)
 Mechanismof action
o Inhibitsproteinsynthesis
o Elicitspremature termination
o Incorporatesincorrectaminoacids
 Activityof aminoglycosidesare impactedbyacidicpH,anaerobicconditions,hyperosmolarity,
and divalentcations.
 IV only,renal elimination
o Eliminationis Tri-phasic
 Alpha,beta,andgamma phases.
 Alpha– distributionof drugfrombloodtotissue
 Beta – eliminationthroughkidney
 Gamma – slow release of drugfrombindingsites(kidneys,ears)
 GOOD penetrationintobone,synovial fluid,andurine
 POORpenetrationintobronchial secretions, CNS(EVENininflamedconditions),eyes,bile,
prostate and purulentfluid.
 Concentrationdependentkilling
o Cmax/AUC:8-10
o AUC:MIC: >100
 Alwayskeeptroughvalues<2mcg/mLtominimize toxicity
 AG therapyshouldbe ONCEDAILY to minimizetoxicity.
 AG’sare ACTIVEagainstmycobacteria,andmanygram positivesandnegatives. However,they
are almostneverusedasmonotherapyand alwaysascombinationtherapy,especiallyin deep-
seatedgram-positive bacteria(endocarditisordevice-relatedinfections).
o An exceptionisthatan AG couldbe usedas monotherapywithaUTI
 Resistance

11. o Enzymaticmodification ismostcommonandis plasmidmediated.
o Decreaseduptake mechanismsare chromosomallymediatedandusuallycross-resistant
to AG’s
 Adverse effects
o NEPHROTOXICITY
 Non-oliguricrenal failure (continuestoproduce urine)
 A slowrise inserumcreatinine isseen alongwithchangesinurine input/output,
and sometimesproteinuria.
 Afterseveral daysof therapy,the AGsaccumulate andcause epithelial cell
necrosis  nephrotoxicity.
o OTOTOXICITY
 Irreversible vestibularandauditory effects
 Can occur duringor afterthe endof therapy
 Can occur withstandarddose or once dailydosing(equal risk);there is
NO SAFEDOSE.
 There is no correlationbetweenpeak ortroughconcentrations,but
increasedriskwithsustainedhightroughconcentrations
 There is no relationshipbetweenserumAGandlevelswithinthe inner
ear.
 Usuallyhighfrequencyhearinglossgoesfirstandmaynot be
recognizedclinically.Low frequencyhearingloss showslossin
conversational hearing.
 GENTAMICINmostvestibulotoxic.
Plazomicin
 Active againstaminoglycoside-resistantisolates(aminoglycosidemodifyingenzymes)
 Active againstESBLs
 Active againstcarbapenem-resistantEnterobacteriaceae
 Has a prolongedpost-antibioticeffect
 Has less gram-positive activitythan the otheraminoglycosides
 PlazomicinisACTIVEagainstgentamicin-resistantEnterobacteriaceae,butactivityis
POORagainstgentamicin-resistantPseudomonas
 Like aminoglycosides,notactive againstStenotrophomonas
 Like otherAG’s,dose isadjustedforimpairedrenal function
 Therapeuticdrugmonitoring:Cmin<3mcg/mLinpatientswithUTI
 Nephrotoxiceffectsdooccur,but tendto occur less.Theyoccur more oftenwithCrCl
<60mL/min and highconcentrationswhere troughvaluesare >3mcg/mL
 Ototoxiceffectsnotobserved,but monitorclosely.

12. Glycopeptides (Vancomycin)
Vancomycin
 Available as IV or Oral
 Exclusively a gram-positive agent:
o Staph (MSSA/MRSA), S. epidermidis
o Strep
o Enterococcus (Faecalis ONLY)
o Corynebacterium
o Listeria
o Bacillus
o C. diff (Oral formulation ONLY)
 The oral form is not absorbed and concentrates in the GI to kill C. diff.
 If using more than 2g/day for >10 days, requires therapeutic drug
monitoring
o Gram positive oral anaerobes (peptostreptococcus)
 MOA:
o Inhibits peptidoglycan synthesis by recognizing D-alanine-D-alanine bonds, and
binding to them. Cell wall cannot form.
 CSF penetration depends on if meninges are inflamed or not.
 Decent lung penetration – enough to kill most bacteria.
 DOSING:
o Empiric: 15mg/kg IV q8-12h, use actual body weight
o Criticallyill:loadingdose of 25-30mg/kg to achieve SSfaster
 Vancomycin requires therapeutic drug monitoring
o Trough goal should be about 15-20mcg/mL
 Check the trough prior to the 4th dose
 Red-Man Syndrome
o A histamine-like reaction that will present with flushing, tachycardia, warmness,
a rash on the face/upper body area, but NOT associated with an allergy.
o It occurs due to rapid infusion of vancomycin.
 Aim to infuse at <10mg/min
 Consider co-administrating with antihistamines
 Pregnancy category B.
 No (few) drug interactions
 Vancomycin is concentration dependent
o Estimate AUC: Total vancomycin dose in 24h / clearance

13. o Goal AUC/MIC to maximize killing: 400mg/L
 More frequently used equivalent is a trough goal of 15-20mcg/mL
 Resistance
o Van A gene will change D-alanine-D-alanine to D-alanine-D-lactate, so
vancomycin won’t recognize the bond.
 Results in VRE
o Staph aureus can pick up the van A gene via plasmids
 Results in VRSA
Lipoglycopeptides (Telavancin, Dalbavancin, Oritavancin)
Telavancin
 Dual MOA – it acts at the cell wall and cell membrane
o 1) Same as vancomycin – interacts with D-ala-D-ala bond at the cell wall
(peptidoglycan)
o 2) Hydrophobic tail penetrates cell membrane, causing it to depolarize and
increases its permeability
 FDA approved for HAP and VAP
 MORE potent than vancomycin for MRSA and MSSA
 ACTIVE against VRE Enterococcus that have VanB (NOTvanA)
 Co-formulated with Hydroxyl-propyl-Beta-cyclodextrin to enhance solubility
 Renal elimination
o Renal adjustmentrequired.Donotuse if CrCl <10mL/min
o Cure rates decreasedforABSSSIswithCrCl <50mL/min
o Watch for renal adverse events/SCr increases
 ADEs
o Taste disturbance (metallic/soapy taste) most common
o CONTRAINDICATED in pregnancy
o CONTRAINDICATED with heparin
o CautionusingotherQT-prolongingagents
o Can prolongaPTT forup to 18 hours (interfereswithphospholipidagentsusedin
measuringthromboplastintime/prothrombintime,aswell asinterferingwith
coagulation-basedfactorXassays)
Long-acting Lipoglycopeptide: Dalbavancin
 Use: ABSSIs
 Gram-positive activity
o VanBand VanCVRE (notVan A)

14. o MRSA/MSSA
o Great for gram-positive anaerobes
o 2 weekhalf-life!–once weeklydosing(ortwice)
 Serumconcentrationscanstay above MIC forovera month
o Reconstitute withONLYWATERor 5% dextrose
o Administerover30 minutes
o Rapidinfusion ->redman syndrome
o N/D/Ha
o No drug-druginteractions
Long-acting Lipoglycopeptide: Oritavancin
 MOST potentof vancomycin,dalbavancin,linezolid,etc.
 ACTIVE against VanA
 ACTIVE against VISA/VRSA
 Half-life8-10days
 Renal elimination,but doesnotrequire renal adjustmentbecause it isclearedveryslowly.
 ONLY administerwith1000mL of D5W
o MonitorpatientswithCHFbecause of such a large volume of fluid
 ONLY administerover3hours
 Artificiallyprolongs apttupto 120 hours
 ArtificiallyprolongsINRandPT (prothrombintime) for12 hours
o Monitoringwarfarin effectivenessunreliable
 Most commonADE:
o N/V/D/Ha
o Limbor subcutaneousabscesses
o MONITOR patientsforosteomyelitis (more casesreportedinoritavancinthan
vancomycin)
 Uses of Dalbavancin/Oritavancin
o Avoidinghospitalization becauseof theirlonghalf livesthatcanremaininplasmafor
overa month
o Minimizingextendedhospitalizationstays
o Preventingneedformultiple IV therapies
 Couldhelpwithcompliance withthose unabletomaintainIV access(e.g.
homeless)

15. Daptomycin (a lipopeptide)
Daptomycin
 Bactericidal
 FDA approvedfor:
o ComplicatedSSSIs
o Staph.Aureusbloodstreaminfection
o Right-sidedendocarditiscausedbyMSSA/MRSA
 DoesNOT coverpneumonia
 DoesNOT coverleft-sidedendocarditis
 POORCSF penetration
 Unique MOA:
o Lipidtail insertsitselfintothe membrane (calciummediated)
o Causesmembrane todepolarize
o Ions(K+) efflux outof the cell,inhibitingproteinandothermacromoleculesynthesis
o  Cell dies,butthe cell doesnotrupture
 Lessof an immune responseiselicitedasaresult
 Spectrumisonlygram-positive:
o MSSA/MRSA
o Enterococci (VRE)
o Strep
o Gram-positive anaerobes
 Renal elimination –considermonitoringSCr
 Dosage isbasedon CrCl andthe type of infection
o Durationof treatmentforcSSSI: 7-14 days
o Durationof treatmentforS. aureusbacteremia:2-6 weeks
o Higherdosesneededforenterococci andpersistentbacteremia
 ONLY administerin 0.9%NaCl (NS) – not compatible withdextrosediluents
 Must infuse at 30 minutes orinject(IV Push) in 2 minutes
 Adverse effectsandwarnings:
o Most commonADEs are N/D/C/Ha
o Warnings:
 Rhabdomyolysisormyopathy
 MonitorCPK levelsatbaseline andweeklythereafter
 Monitoror holdforpatientstaking HMGCoA reductase inhibitors
 Discontinue daptomycinif myopathyispresentandCPKis> 5X normal
(1000 U/L)
 Discontinue daptomycinif patientisasymptomaticandCPKis10X
normal (2000 U/L)
 Eosinophilicpneumonia
 Occurs 2-4 weeksafterstartingdaptomycin
 Improveswithdiscontinuationandsteroidtherapy

16.  Suspecteosinophilicpneumoniainpatientswithfever,hypoxia,or
pulmonaryinfiltrates
 No druginteractions
 Daptomycincan cause false prolongationof INRandPT withsome thromboplastin reagents.
 Resistance inEnterococci andS.aureus:
o Mediatedby dltA gene
 Causeschangesincell membrane permeability;cell membrane haslessaffinity
for daptomycin
o Mutationsingenesassociatedwithphospholipidsynthesis
Oxazolidinones (Linezolid, Tidezolid)
Linezolid
 BacterioSTATIC
 Linezolidbindsinhibitsproteinsynthesisbybindingtothe 50s ribosome peptidyltransferase
center(PTC;the 23s rRNA) and stoppingthe growthof bacteria. Blocksthe formationof 30S and
50S ribosome complex.
 The acetamide groupof linezolidcausesareductioninitsactivity
 Spectrumisgram-positive
o MSSA/MRSA
o Enterococcus(VRE)
o Strep
o Gram-positive anaerobes
o MycobacteriumandNocardia
 FDA approvedfor:
o VRE
o Nosocomial andCA pneumonia
o UncomplicatedandcomplicatedSSSIs
 IV and PO bothhave 100% F
 NO renal or hepaticadjustmentneeded
 GOOD CSF penetration
 Adverse events:
o Myelosuppression
 Thrombocytopenia>anemia> neutropenia
 Usuallyhappensafter> 2 weeks of use
 Performa weeklyCBC
o Opticneuritiswithuse >28 days
o Peripheral neuropathywithuse >28 days
 Interactions:
o None,butcan act as an MAOIinhibitor

17.  May interactwithserotoninergicagents,MAOIs,andtyramine-containingfoods
 May cause serotoninsyndromewithin6hoursof use
 Mental status changes,hyperreflexia,shivering,fever,diarrhea,tremors
 Resistance:
o Mutationsof the 23s rRNA (the portionof the 50S that bindsthe 30S subunit)
o cfr gene can cause resistance inEnterococci andStaph. aureus
Tedizolid
 A PRODRUG
 A phosphate modificationincreasessolubility,bioavailability,and limitsthe reactionwithMAOIs
o Whenthisphosphate iscleavedandreplacedbyanOH group, it remainsactive against
cfr genes!
 Tedizolidhastwoextraringsthatallow tighterbinding(greater potency) tothe PTC (the 23s
rRNA) of the 50s subunit.
 Same MOA as linezolid –preventstranslationof proteins.
 Usedfor ABSSSIs;treatmentduration6days
 More potentthanlinezolidineveryway andretainsactivityagainstlinezolid-resistantMRSA
 Like linezolid,bacteriostaticand100% F, and NOadjustmentsforrenal orhepaticimpairment
 Possibly WEAKERinteractionwithMAOIsthanlinezolid
o Evidence islackingsince theyexcludedpatientstakingMAOIsintheirtrials
 Most commonADE is Nausea
 TidezolidRETAINSACTIVITYagainst VREandlinezolid-resistantMRSA that have the cfr gene
Tetracyclines and Glycylcyclines
 Tetracyclines (Tetracycline, doxycycline, minocycline, Eravacycline, Omadacycline)
 Glycylcyclines (Tigecycline)
All tetracyclines
 BacterioSTATIC
 NONEhave activityagainstPseudomonas
 Entry intocell and MOA:
o Gram-positives:EnterviapH-dependentactive transport
o Gram-negative:Enterviaporinchannels
o Inhibitsprotein synthesis andelongation byactingonthe 30s subunit
 Active againstvariousatypicalslikeparasites/spirochetes
 ADEs:
o GI side effects:N/V/D/Heartburn/Epigastricpain

18. o Photosensitivity&Hyperpigmentation
 Blue-blackdiscolorationoccurs inscars/inflammation
 Muddy-brownpigmentoccursonsun-exposedareas
 Use sunscreenandprotective clothing
o Teethcan become yellow/gray/brown;permanent
o Bone growth can be inhibitedininfants/childrenunder8y/o
 Reversible
 Avoiduse
o Nephrotoxicity
o Neurotoxicity
 Neurototiceffects seenmore in minocycline(dizziness,vertigo,tinnitus) and
these effectsare seenmore ofteninwomen
 Pseudotumorcerebri canalsooccur(highpressure thatdevelopsinbrainand
mimicsa tumor)
o AVOIDIN PREGNANCY - can cross placentaandhave toxiceffectsonfetus(retard
skeletal development) –thiseffectgoeshand-in-handwithitsotherbone growth
inhibitioneffect.
 Reducedriskof C. diff infection
 Interactions:
o CATIONS(di/trivalent) reduceabsorption
 Take 1-2 hoursbefore or 2 hours after
 Buzz word:multivitamin
o Oral anticoagulants:
 Increase bleedingriskbydecreasingvitaminKproduction
o Oral contraceptives
 Reduce birthcontrol drug levels
 Use mechanical meansof contraception inadditiontoBC
Tetracycline
 IV formulation nolongeravailable due tohepatotoxicity
 AVOIDIN RENAL IMPAIRMENT
 Can cause hepatitis
 All tetracyclineshave alonghalf-life exceptTetracycline
 HIGHEST renal elimination
 TAKE ON AN EMPTY STOMACH, foodreducesabsorption50%
Doxycycline
 IV and PO

19.  100% F
 SAFEin renal impairment due tohighfecal excretion
 DoesNOT cause hepatitis
 ADEs:
o Pill esophagitis
 Take with8oz waterandstay uprightfor 30 minutes
 Carbamazepine,phenytoin,andbarbiturates DECREASEhalf-lifeof doxycycline,thusdecreasing
itstherapeuticeffect.
Minocycline
 IV and PO
 100% F (slide says90% to be specific,butIV andPO conversionsare 1:1)
 Doesnot needrenal orhepaticadjustment
 LOWEST fecal elimination
 ADEs
o Long-termuse of minocycline cancause blue-blackgumdiscolorationdue to bone
pigmentation underthe gums
Tigecycline (Glycylcycline)
 Sterichindrance allowstigecycline toovercome efflux pumps andribosomalprotection
 Most common ADEs: Nausea/Vomiting
 NO dosage adjustmentinrenal impairment
 Adjustforsevere hepaticimpairment: 25mgIV q12h vs typical 50mg IV q12h
 DO NOT USE for bloodstreaminfections/bacteremia
o Drug’sVd ishighand binds tissuesverywell–leavingserumconcentrationsverylow
 Uses:
o CAP
o Complicatedintra-abdominal infections
o Complicatedskinandskinstructure infections
 WARNING:
o Mortalitywas HIGHER withtigecycline use. Onlyuse whennootheralternativesare
available
 Resistance toTigecycline:
o Tet genes – plasmidmediated
o Efflux pumps (grampositiveandnegative)

20. o Ribosomal protectionproteins
Omadacycline
 IV or PO
 LOWEST renal elimination
 LOWEST proteinbinding
 Uses:
o CAP
o ABSSSIs
 ADEs:
o Transaminitis,hypertension,insomnia,gastrointestinalupset
Eravacycline
 Use: Complicatedintra-abdominalinfections
 If usinga strongCYP3A inducerconcomitantly,Eravacyline’sclearanceisincreased.
o UP DOSAGE to 1.5mg/kgq12h
 DO NOT USE Eravacycline forcomplicatedUTIs
o In clinical trialsitdidnotshow statistical non-inferiorityvsErtapenem
Sulfonamides (Bactrim)
TMP/SMX (Bactrim)
 Sulfonamidesare analogsof PABA
o Competitivelyinhibitsdihydropteroate synthase,reducingdihydropteroicacid
concentrations
 Trimethopriminhibits dihydrofolate reductase,reducingtetrahydrofolateconcentrations
 Almost100% F
 Available asoral/oral suspension/IV
 Dosage dependsonthe infection
o Dosage isbasedon trimethoprimcomponent
o Use adjustedbodyweight forobese patients
 ADJUST forrenal dysfunction
 TMP/SMX is FIRSTLINE for:
o Nocardia

21. o Stenotrophomonas maltophilia
o B. cepacian
o Pneumocystisjiroveci
 CoversMSSA/MRSA
o Beta-lactamsmore effective forMSSA
 DoesNOT coverPseudomonasorenterococcus
 NO anaerobicoratypical coverage
 Resistance:
o Permeabilitybarriers/efflux
o Alteredbindingtodihydrofolatereductase (trimethoprim)
o Alteredbindingtodihydropteroate synthase (sulfonamides)
o Resistance canbe transferredtootherorganisms
 Pregnancy category D
 ADEs
o Most commonside effectsare GI related:N/V/D/Anorexia
o Hyperkalemiacanbe causedby TMP (ithasa potassium-sparingeffect)
o IncreasedSCrfromTMP, butfiltrationisnotaffected
o Interstitial nephritisorcrystalluria fromsulfonamide
 Interactions
o TMP:
 Dofetilide
 Phenytoin
 Warfarin
 Digoxin
o SMP:
 Nephrotoxicagents
 Methenamine –Avoid
 Elvitegravir
 Sulfadiazine (adifferentdrugthanTMP/SMX) is usedfortoxoplasmosis
Fluoroquinolones (Ciprofloxacin, Levofloxacin,
Moxifloxacin, Gemifloxacin, Delafloxacin)
Ciprofloxacin
 Of the fluoroquinolones,ithaslowerFthanmost (exceptDelafloxacin)
 Of the fluoroquinolones,itshalf life isthe lowest(alongwithDelafloxacin) –needsBIDdosing
vs.once dailyforothers.
 Renallyeliminated
 Thinkgram-negatives(Pseudomonasincluded)
 Ciprospecificdruginteractions(duetoitsCYP1A2 inhibitionpotential):

22. o Theophylline–increaseslevels.AVOIDconcomitanttherapy
o Cyclosporine –increaseslevels
o Methotrexate –inhibitsrenal tubulartransport
Levofloxacin
 Of the FQ’s, has the HIGHEST renal elimination. Best for urinary penetration.
 BEST for lung penetration. Think strep pneumo and respiratory infections.
 Covers PSEUDOMONAS
 Covers MSSA (not MRSA)
Moxifloxacin
 Of the FQs, LOWEST renal elimination. Not useful for UTIs
 Of the FQs, HIGHEST half-life
 2nd best for lung penetration. Think strep pneumo and respiratory infections.
 Covers ANAEROBES
 Covers MRSA
 Does NOT cover pseudomonas
Gemifloxacin
 Low renal penetration. Not useful for UTIs.
Delafloxacin
 Of the FQs, LOWEST oral bioavailability
 Like Levo and Moxi, FDA approved for CAP
 FDA approved for acute bacterial skin and skin structure infections
 Covers ANAEROBES
 Covers PSEUDOMONAS
 Covers MRSA
 The only FQ that Covers E. Faecalis (not) faecium
 Does NOT produce QT prolongation effects
 Package label states that FQs should be used when there is no alternatives for all FQs
EXCEPT Delafloxacin

23. Macrolides (Erythromycin, Clarithromycin, Azithromycin)
Erythromycin
 WORST gram-negative activity (A>C>E)
 Oral base formulation needs enteric coating. Esters are more
resistant/better absorbed.
 The BEST absorbed erythromycin ester oral formulation is
erythromycin estolate.
 Don’t take any erythromycin EXCEPT E. estolate with food
(does not effect estolate version)
 Absorbed in duodenum
 Minimal distribution into CSF. Highly protein bound.
 NO adjustment required in renal impairment (bile and fecal elimination)
 Crosses placenta/into breast milk
 Erythromycin is the ONLY approved macrolide for Diptheria infections
 Unique off label use – Gastroparesis (prokinetic agent)
 Of the macrolides, has the GREATEST chance of causing
hepatotoxicity (starts 10-20 days after treatment [long term
use])
 Strongly inhibits CYP3A4
Clarithromycin
 Has a methoxyinstead of a hydroxyatC6
 Clarithromycinasa parentdrugis active,andit alsohas an active metabolite.
 BEST gram-positive activity(C>E>A)
 Resistance foundinmycobacterium&H. pylori
 The onlymacrolide (atleastfromlecture) NOTavailableIV
 Firstpass reducesFto 50-55% (HIGHEST F)
 May be givenWITHor WITHOUT food
o Give ER versionswithfood,though.
 Metabolizedbythe LIVER.MetabolismisSATURABLE.
o Higherdosesequate tolongerhalf-lives

24.  20-40% excretedinurine.ADJUSTdose if CrCl < 30mL/min
 NO dosage adjustmentw/hepaticimpairment
 GI, cardiac, andhepatotoxiceffectsLESSthanerythromycin
 Use withH. Pylori infection
 Use withMycobacterial infections(M.leprae andM.AviumIntracellulare)
 Use withResp.tract infections
 Like erythromycin,stronginhibitorof CYP3A4
Azithromycin
 Instead of 14 membered rings, has 15 carbon ring.
 Has a nitrogen in place of carbonyl group at 9a (in place of ketone found in
erythromycin)
 WORST gram-positive activity (C>E>A)
 BEST gram-negative activity (A>C>E)
 Absorbed rapidly but incompletely (F=30-40%)
 Has high drug concentrations within cells
 Excreted via biliary route
 Very little (12%) excreted in the urine
 Has the LONGEST half life (40-68h) due to its tissue binding ability
 GI, cardiac, andhepatotoxiceffectsLESSthanerythromycin
 Of the Macrolides, Azithromycin is preferred in resp. tract infections
o Chlamydia, pertussis, mycobacterial infections
 Z-pak dosing: 500mg PO day 1, then 250mg PO day 2-5
 A single 1g dose can be given for uncomplicated gonococcal
urethritis due to C. trachomatis.
 LOWEST likelihood of the macrolides to cause drug interactions
Fosfomycin
Fosfomycin
 F is low – use limited to UTIs (bladder infections; cystitis)
 Enters the cell via two active transport mechanisms:
o Glycerophosphate transport (GLpT)
o Hexose phosphate uptake system(UhpT)
 Blocks cell wall synthesis; bactericidal
 Binds the MurA enzyme by acting as a phosphoenolpyruvate analog and blocks the
initial step in peptidoglycan synthesis.

25.  Oral ONLY
 Short half-life, renal elimination
 Active vs MSSA/MRSA/Enterococcus
 NOT ACTIVE against S. Saprophyticus, Stenotrophomonas, Burkholderia, anaerobes
 Resistance
o MurA alterations
o Overexpression of enolpyruvyl transferase – overpowers Fosfomycin activity.
o Transport alterations (remember it has to get transported by GLpT & UhpT )
o Fos A, Fos B, Fos C (Fosfomycin modifying enzymes)
 GI: Diarrhea/nausea most common
 Interactions:
o Drugs that stimulate motility decrease absorption of Fosfomycin
o Fosfomycin might minimize aminoglycoside accumulation.. less nephrotoxicity?
 Uses:
o Uncomplicated acute cystitis
o Complicated cystitis
o Prophylaxis
 It is expensive
Nitrofurantoin
Nitrofurantoin
 Macrobid (macrocrystalline) is more tolerable than microcrystalline (less D/N)
 Has short half-life and is eliminated in urine and bile
 Alkaline urine may reduce its effectiveness
 It relies on concentrating in the urine to work, so impaired renal function may have
limited effectiveness
 It does not penetrate well into kidneys, CSF, eyes etc. Only useful for bladder infections
(cystitis)
 Take with food!!
 Technically contraindicated in CrCl <60ml/min but still used at 40+ mL/min
 CONTRAINDICATED in pregnancy >38 weeks and neonates <1 month
 ADEs
o GI: N/V (dose related)
o Pulmonary toxicity/fibrosis with long-term use

26. o Urine discoloration (brown)
o False positive glucosuria test
o Magnesium antacids (reduces nitro absorption)
o Probenecid (increases Nitro serum concentration)
 Only for cystitis, typical treatment duration 5 days. Primarily GI sx.
 Consider Fosfomycin for long-term use (prophylaxis)
Polymyxins (Colistin, Polymyxin B)
Colistin
 IV or inhalation only (inhalation optimizes lung exposure)
 Poor penetration to lung, tissue, pericardial fluid, CSF
 Colistin is given as an INACTIVE PRODRUG (Colistimethate sodium, CMS)
o CMS gets cleared by renal elimination OR converted to Colistin (active)
 Colistin is eliminated by non-renal clearance – the high concentrations found in urine
are CMS being converted to colistin.
 Because of being found in urine, it is BETTER than polymyxin B for UTIs
 Colistin requires a loading dose to be used
o When calculating dose, CrCl is calculated with Jellife equation
o Actual or ideal BW is used, whichever is lower
Polymyxin B
 IV only
 NON-renal elimination
 Unlike colistin,administeredinACTIVEform
 Gets REABSORBEDinkidney,resultinginlow urinaryconcentrations;notuseful forUTIs
 Dosingmustbe adjustedforrenal function
 Of the two,consideredmore reliabledue tobeingadministeredinactive form
Lincosamides (Clindamycin)
Clindamycin
 BacterioSTATIC(likemacrolides)
 Inhibitsthe 50S subunit(likemacrolides)
o Inhibitspeptide bondformation(inhibitstranslocation,likemacrolides)

27.  Spectrumisgram-positive andanaerobes
o Strep,MSSA/MRSA
o Anaerobes:bacteroides,prevotella,fusobacterium, Clostridium
 C. perfringensonly,NOTC.Difficile
o Pneomucystis jirovecii (fungus)
o Protozoa(Toxoplasmagondiiandplasmodiumfalciparum)
 Resistance toclindamycin(sameasmacrolides) –ermgene..methylatesadenineof 23s RNA of
the 50s subunit.Thiscan be constitutive orinducible.
o Thus,cross resistance to macrolidesandclindamycinandstreptograminB
o Phenotypically,bacteriawiththisgene wouldbe called“MLSB”
o Resistance isplasmidmediated.
 The D test(forStaph – onlystaphhave the ermgene.Strephave the mef gene)
o Thistestis useful whenyour staphisolate iserythromycinresistantandclindamycin
susceptible.
 If this occurs,you needtoperforma D-test.
 D-testresultpositive:Staphcanbecome resistanttoclindamycinduring
therapy.Do notuse.
 D-testnegative:Canuse clindamycinfortherapy.
 Oral formnearlyCOMPLETLEY absorbed(availablePO/IV/IM,andtopical)
 Penetratesmostfluid/tissuesEXCEPTCSF
 Clindamycinismetabolizedbythe liverandthusmay ACCUMULATE in severe hepaticfailure
 AfterIV therapystopped,antimicrobialactivity canpersistinfecesfor>5 days
 NO ADJUSTMENT inrenal failure orhepaticdisease –monitor
 Uses:
o SSTIs(INCLUDINGCA-MRSA)
o Respiratorytractinfections(due toitsanaerobicactivity)
 Abscesses,anaerobicpleuralspace infections
o Otheranaerobicinfections
 (infectionsof the female genital tract)
 Prophylaxisof endocarditisinpatientswithvalvulardiseaseundergoingcertain
dental procedures(pts.Withpenicillinallergies)
o WITH primaquine,alternative agentforpneumocystisjirovecii pneumonia
o WITH Pyrimethamine,AIDS-relatedtoxoplasmicencephalitis
o Surgical prophylaxis
o Topical formfor acne vulgaris,bacterial vaginosis
 ADEs
o GI: N/V/D;mostlywithPO
o Big riskforC. Diff infection
o May blockneuromusculartransmission
o Weighbenefitvsriskin pregnancy
o AVOIDwhile breastfeeding

28. Nitroimidazoles (Metronidazole)
Metronidazole
 INERT (prodrug) until activatedinthe cell
 MOA:
o 1) Drug ENTERS the cell viapassive diffusion
o 2) An ELECTRON TRANSFERto metronidazole’snitrogroupoccurs.
 Resultsin a reactive free radical
 The free radical INTERACTSWITH DNA
o 3) DNA synthesisisINHIBITEDanddamaged.Oxidation,breaks.Etc.
o 4) DNA DEGRADES,host cell DIES.Thenthere isa RELEASE of INACTIVEENDPRODUCTS
of the drug.
 ANAEROBESONLYdoes not work inaerobes
o MainlyBacteroides(lowresistance)
o Can alsobe usedfor parasiticinfectionsandH pylori
 Oral caps/tabs,IV,topicals(creams/gels/lotions/vaginalgels)
 NO dosage adjustmentinrenal impairment
 50% dose reductioninsevere hepaticimpairment
 100% F; IV to PO conversion1:1
 Proteinbinding<20%, lowproteinbindingandverylipophilic.
 Large Vdmakesit effective forgettingintotissues
o PREFERRED AGENT FOR CNSANAEROBICINFECTIONS
 ADEs
o CNS(ataxia,encephalopathy,seizure,asepticmeningitis)
o Peripheral neuropathy(w/prolongeduse,reversible.Mostcommon)
o Disulfiram-likereaction(Antabuse reaction)
 SAFEpregnancy;deferbreastfeedingif takinglarge dosesof metronidazole
 Bacteroidesresistance:nimgenes