C diff exotoxins are associated with
Toxin A: activates inflammatory cells that release cytokins
cause increase in permeability and loss of fluids
toxin B cytotoxins
cause further damage of GI mucosa after initial damage of toxin A
Name risk factors for C Diff
abx use (broad spectrum)
long term exposure or exposure to antimicrobials
age > 65
immune suppression
PPI/H2RA (increase acidity and more prone to c diff)
female
gi tract manipulation
S/Sx of C Diff
>3 unformed stool in 24h severe abd cramps/pain n/v fever anorexia malaise
serious compl:
pseudomembranous colitis
toxic megacolon
Name high risk abx associated with C Diff
clinda
extended spectrum cephs
FQ
aminopenicillins (amox/ampic)
name moderate risk abx associated with c diff
bactrim
macrolide
pcn
name low risk abx associated with c diff
vanco
AMG
flagyl
Is probiotics recommended to use for ppx/tx of c diff
Is loperamide recommended to be used for diarrhea?
limited data
no, data lacking
Classification of tx of of C diff
Non severe: WBC < 15000 AND Scr < 1.5
Severe: WBC > 15000 OR Scr >1.5
Fulminant: hypotension or shock ileus, megacolon
tx of c diff (1st episode)
non severe: vanco 125mg qid x10 days or
fidaxomicin 200mg bid x10d
may use flagyl 500mg tid x10d only if above agents not available
severe: vanco 125mg qid x10d or
fidaxomicin 200mg bid x10d
fulminant: vanco 500mg qid PLUS
metronidazole 500 IV q8h
add rectal vanco if ileus is present
tx of first recurrent c diff
if metronidazole was used initially: vanco 125mg qid x10d if standard vanco was used: prolonged or pulsed vanco vanco 125mg qid x10 then 125mg bid x7then 125mg qd x7 then 125mg q2-3d x2-8 weeks or fidox 200mg x10d
tx of 2nd or subsequent recurrence
- pulse or tapered vanco
- 125mg qid x10 followed by rifaximin 400mg tid x20days
- fidox 200mg bid x10d
- fecal microbiota transplantation (FMT)
cephalosporins MOA
time dependent does not depend on immune system bactericidal time > MIC inhibits cell wall inhibit PBP
Cephs covers PSA
gen 3: ceftazidime
gen 4: cefipime
gen 5: ceftolozane/taz
ceftaz/avibactab
cephs covers MRSA
ceftaroline
cephs covers ESBL
ceftolozane/tz
ceftaz/avibactam
cephs with good penetration to CNS
cefuroxime cefotaxime ctx ceftaz cefipime
Carbapenems general info
inhibit PBP works on ESBL ( E coli and Proteus) works on PSA (except ertapenem) No coverage for enterococcus or MRSA IM option only for ertapenem
Specs on carbapenems
doripenem (Doribax)
ertapenem (Invanz) - not effective for PSA, required dose adjustment on CrCl < 30, QD dosage, IM/IV
imipenem/cilastin (Primaxin) - associated with high risk of seizure activity, cilastatin protecs kidneys from nephrotox
meropenem (merrem) - 2nd for risk of seizure
monobactams
Aztreonam bacteriocidal inhibit PBP MONObactam - covers only one type of bacteria - gr - PSA coverage available in IV/Nebs (cayston) SE: phlebitis and liever enz elevation
Glycopeptides and lipoglycopeptides
drug list
MOA
SE vanco
vanco
telavancin
dalbavancin
oritavancin
Mainly covers MRSA and enterococcus
MOA: binds to D-alanyl-D-alanine and blocks glycopeptide polymerization (discrupt cell wall linkage)
Time dependant
BacterioCIDAL
VRE - D-alanyl-D-alanine changed to D-lactate - decrease affinity
Dalba and Orita - both have long t1/2 and and D5w only
Vanco - use ABW
SE vanco: infusion rate rash
nephro and ototox
thrombophlebitis
fosfomycin
bacterioCIDAL
inhibit cell wall synthesis
gr - (E coli)
enterococcus sp
macrolides gen info
list of drugs
concentration dependent
AUC/MIC
bacterioSTATIC
works on 50S ribosomes
azithromycin - available IV/po
clarithromycin - po, cyp3a4 I moderate, QT prolongation, gi se
erythomycin - po/iv, major CYP3A4 I, qt prolongration, GI se
list of biacterioSTATIC drugs
ECSTaTIC about bacteriastatin erythromycin clarithromycin sulfamet trimetoprim tcn chloramphenicol
list of drugs that work on 30S/50S ribosomes
buy AT 30, CCELL for 50 dollarS
30: AMG and TCN
50: clinda, chloramphenicol, erythom, linezolid, lincomycin, streptomycin
with exception to linezolid and AMG - all are bacteriostatic
Which bacteria does macrolide cover?
gr+
gr - (incl leionella pna and MAC)
atypical (mycoplasma pna)
drugs that have good intracellular penetration
macrolides, FQ, TCN
which macrolide is used to treat H Pylori
clarithromycin
which macrolides have CYP3A4 interactions
clarithromycin (moderate)
erythromycin (major)
findoxomycin (Dificid)
macrolide, but inhibit protein sysntesis (not 50s)
only for C Diff
Which macrolides that may cause QT prolongation
erythromycin and clarithromycin
possible azithromycin
PCN parameters
bacteriocidal (kill on its own)
does not depend on immune system
time dependent
time >MIC
MOA of PCN
BL abx inhibit cell wall synth in bacteria by inhibiting enzyme transpeptidase (PBP) => cell lysis
peptidoglycan of bacterial cell wall
pcn covers
GR + strep pyogenes strep viridans strep pneumo (some) GR - N meningidis Pateurella multocida Anaerobs: clostrodium sp syphilis
NOT used for staph aureus
PCN SE
n/v/seizures
HyperK with aq PCN G
rash/anaphylaxis
Combo PCN Probenecib
decrease renal excretion, increase AUC
Penicillinase resistant PCN (PRP) drugs
dicloxacillin
oxacillin
nafcillin
PRP covers
narrowed to staph aureus and staph epiderm
MSSA
NO gram -, no MRSA
not for strep
which PRP renally excreted
oxacillin
PRP used for
skin and tissue infection
endocarditis (may be used with AMG for synergy)
Aminopenicilllins drugs
amox
ampicillin
Aminopenicillins coveres
more hydrophilic
exp gram - : H infl, E coli, Proteus
good activity against PCN resist pneumococci, enterociccus, Lysteria
some anaerobs
Beta lactamase Inhibitors drugs
avibacatm
clav acid
sulbactam
tazobactam
BL inhibitors covers:
NO PSA:
augmentin
unasyn
PSA: zosyn, ceftaz/avibactam, ceftolazone/tazob
ESBL: ceftaz/avibactam, ceftolazone/tazob
if sending home with PSA: cipro, levo, oxflox, noflox
Gr +, Gr-, anaerobs, PSA and ESBL
TCN general characteristics
Protein systensis Inhibitors
concetration dependant
AUC/MIC
bacteriostatic (ECSTaTIC about bacteriostatic)
inhibits 30S (buy AT 30 CCELL 50 dollarS)
require immune to work
includes: tcn minocycline doxycycline tigecycline
avoid in peds < 8yo
TCN specs and SE
TCN: oto/nephrotoxicity, phototoxicity, GI esoph ulcirations (with full glass of water)
Doxicycline: coveres MRSA, phototoxicity, may give with good
Minocycline: CA MRSA, empty stomach
may cause Idiopathic intracratnial HTN
Which TCN must be renally adjusted
mino and TCN
TCN discoloration
yellow - TCn
blue- mino
General info on Glycylcyclines
Tigacycline (Tigacil)
iv only
used when AKI/ARF and TCn can be used
Soft skin infection
Gr +: MRSA
Gr -
atypical
increased mortality when use off label
List all drugs that are protein synthesis inhibitors
macrolides ketolides tcn glycylcyclines anaerobic agents linezolid streptogramins aminoglycosides
list of drugs in oxazolidinones drug class
linezolid (zyvox)
tedizolid (sivextro)
General specs on oxazolidinones
bacteriostatic if treating enterococci and staphylococci
bacteriocidal if trep pneumo, b fragilis and c perfrigens
MOA: inhibit assembly of bacterial 23s of 50s subunit => prevent formation of 70s comples
have MAO propertioes => caution with serotonin syndrome
oxazolidinones coverage
MRSA
MDRSP
VRE faecium
VRE faecalis
oxazolidinones drug info
linezolid: po/iv compatible in d5w,ns,lr good bioavailability report myelosuppresion and thrombocytopenia if >2wk
given for: soft tissue inf CAP HCAP/HAP enterococcal
Tidezolid: skin soft inf ONLY given qd over 1 hr iv only ns only
myelosupression with linezolid
> 2wks
reversable
if >4wks lactic acidosis and peripheral neuropathy
drug class streptogramins
quinopristin/dalfopristin (30/70%)
MOA: binds to 50s
buy AT 30 CCELL at 50S
AMG, TCN. Clinda, chloamph, erythrom, linezolid, lincomycin, streptogramins
Coverage: VRE (not e faecalis (compare to linezolid)
MRSA
MDR Strep pneumo
Dosing: VRE: 7.5mg/kg IV q8h
Soft skin: 7.5mg/kg IV q12h
ADJUST hepatically
SE: phlebitis (PICC LINE ONLY) , hyperbilirubin, may use buffer (D5W), flush line before and after!
list of drugs for AMG
amikacins gentamicin tobramicin neomicin streptomicin
Specs on AMG
cocncetration dependant
longer the exposure the higher the risk of SE
peac/MIC
bacterioCIDAL
Very vanco Finely FQ Proficient PCN At AMG Cell cephs Murder metronidazole
MOA: binds to 30 and 50S
SE: nephrotoxicity
otic drops used only for otitis externa (swimmer ears)
AMG covers
good gr _ (PSA and serratia)
gr+ little staph aureus
dosing
must monitor peak and trough
gent + tobr: traditional
high peak - 1.5-2mg/kg q8h
lower peak 1-1.5mg/kg
use IBW or ABW in obese
amik: 5-7mg/kg q8h
renally adjusted:
>90 q8h
50-90 q12h
<50 q24h
extended interval - qd dosing - use random level to monitor 6-10 hours AFTER the dose - then use chart to adjust frequency
AMG drug info:
neomicin - top or po, po not abs, used for hepatic enceph
amikacin - IV/IM - dosing ext and trad same
tobra/gent - IV/IM, gent nebs -
1.5-2mg/kg q8h or
ext 5-7mg/kg/day (dicrease se profile)
streptomicin - emergency prep IM
FQ gen info
bacteriocidal
concentration dependent Very vanco Finely FQ Proficient PCN At AMG Cell cephs Murder metronidazole
MOA: work on DNA gyrase (inhibit topoisomerase II)
DDI - di and trivalent
Coverage: PSA (cipro and high dose of levo/nor/oflox
good atypical coverage
NO UTI for gemi and moxi
drug info on FQ
delafloxacin - covers MRSA
cipro - po/iv PSA
not good for strep pneumo
nor/oflox - PSA
levo - PSA high doses
moxi/gemi - no UTI, no PSA,no MRSA
SE FQ
all - QT prolongation increase sizure risk with NSAID tendon rupture (increased with >60yo+steroids)
Clinda and lindomycin
protein synthesis inhibitors
bacteriocidal and static
gr+ anaerobic inhibit 50S compete with macrolide covers CA MRSA great for alt PCN
SE: c diff
diarrhea/n/v
neutropenia
hepatotoxicity
metronidazole
bacteriocidal
rpodrug
gr - anaerob
se periopheral neuropathy
metalic tste
weak 2c9 i (warfarin)
Uti diagnosis
Urinalysis: Bacteria Wbc and leukocyte estrerase Rbc (more systemic) Nitrites: (dicreased) Ecoli Klebsiela Proteus
Other bugs will not produce nitrates
> 100 000 one pathogen
Uti treatment options
Nitrofurantoin Bactrim Fosfomysin Fq Beta lactams
daptomycin
using Ca and insert into bacterial membrane
concentration dependant
bacteriacidal
MRSA
NOT FOR PNA - will bind to surfactant
monitor Ck/myopathy
Bactrim
bacteriocidal
se bone marrow supression
pancreatitis
MRSA
major 2C9 inhibitor (warfarin)
substrate 3A4 and 2C9
Nitrofurantoin
cell wall inhibitors
probenecid may inhibit excretion
se peripheral neuropathy
RF for UTI
female gender immunosenescence hormonal changes neurologic disease BPH DM personal hygiene
UTI Sx
acute: localized
pyelonephritis: systemic s/sx increase WBC fever flank pain n/v malaise
both may have altered mental status, behavioral changes, and change in eating habits
UTI pathogens
Ecoli
Klebsiella and Proteus
Complicated:
Gr- : PSA as a MDR
GR+: MRSA or VRE
name two types of PNA
CAP
HAP : occurs >48h of hospitalization, includes MDR
Criteria to admit outpt to hospital due to PNA
use CURB65 Confusion Uricemia (BUN >20 RR >30 BP SBP<90 and DBP <60 65 yo >/=
2+criteria
Diagnosis of PNA
CXR
sputum and blood cultures may be considered but often do not yield positive results, used primarily in hospital
urine sample good for Legionella and Streptococcus antigens
RF and comorbidities to assess MDR for PNA
comorbidities: chronic Lung, Liver, Renal dz DM OH asplenia malignancies/immunosupression/meds
RF: comorbities OH use daycare immunosupressive drugs >65 abx within 3m
CAP treatment
outpt:
macrolides OR doxycicline
outpt with comorb OR RF for MDR:
macrolides with b-lactams
OR
respiratory FQ
inpt, non ICU
macrolides with b-lactams
OR
respiratory FQ
inpt, ICU macrolides with b-lactams OR respiratory FQ consider MRSA +/- PSA