Unit 1- Bacterial Infections

ABX classes that target Bacterial cell wall/membrane

Beta-lactams (Pens, Cephs, Penems), Fosfomycin, Vancomycin

ABX classes that have DNA/RNA targets

FQs, Bactrim, Macrobid, Metronidazole, Mupirocin, Rifampins

ABX classes that inhibit Protein synthesis

Macrolides, Clindamycin, TCs

Where do Beta-lactams inhibit cell-wall synthesis and what proteins?

Stage 3 of cell wall formation, inhibits trans-peptidase and trans-glycosylase

In general, what pathogens do Beta-lactams kill and why?

Bacteria, peptidoglycan containing cell walls!

Which bacteria ususally are not susceptible to Penicillins and why?

acid-fast bacteria (unusual cell wall), mycoplasma (no cell wall), rikettsia/chlamydia (intracellular pathogens)

Things needed for a penicillin to be effective

distribute to site well, penetrate to target site of action, must have affinity for PBPs, not be inactivated by BLs

Penicillin resistance mechanisms and what bugs mainly do that?

Modification of target PBPs (MRSA and PRSP), production of BLs (S. aureus and most GNB), impaired drug penetration and even efflux (Some GNB)

How can we combat BLs with Penicillins?

Use BLIs in combination (clavulanate, tazobactam, sulbactam)

Penicillin activity vs Streptococci and Enterococci

All active against susceptible strep, ASPs are not active against enterococci, Pen G and Ampicillin most active against enterococci

Penicillin activity vs Staphylococci

BLs of MSSA inactivate all penicillins; ASPs and penicillins combined with BLIs are effective; MRSA is not susceptible to ANY penicillin

Penicillin activity vs Moraxella and Neisseria

Usually needs Pen + BLI due to BLs

Penicillin activity vs Enterobacteriaceae

ESP + BLI if it doesnt produce ESBLs

Why are oral penicillins given in water soluble salts?

allow easier dissolving and more rapid absorption in GI tract

T or F Penicillins have good Distribution?

True

How are most Penicillins excreted and what is the exception?

renally, ASPs cleared both renal and biliary, nafcillin cleared by biliary only

What is the goal in terms of drug concentration for Pens?

amount of time above MIC, aka extend the length of time at therapeutic levels

Differences in CSPs compared to Pens

greater stability, greater BL stability, broader spectrum

FGCs

cefazolin, cephalexin, cefadroxil

SGCs

Cefuroxime, cefuroxime axetil, cefprozil, cefmetazole

TGCs

Cefotaxime, Ceftriaxone, Cefdinir, Cefditoren, Ceftibuten, Cefpodoxime proxetil, Ceftizoxime, ceftazidime

4th Gen CSPs

Cefepime

5th Gen CSPs

Ceftaroline, Ceftobiprole

FGCs activity

Mainly against susceptible Staph/Strep

SGCs Activity

Same as FGCs plus Respiratory GNBs and other simple GNBs

TGCs Activity

Same as SGCs plus most other NSBL and BSBL producing GNBs

5th Gen CSPs best for?

killing MRSA

Primary ADRs for Pens and CSPs

Hypersensitivity reactions, Seizures, GI intolerance

Use for carbapenems

Second-line therapy, kills a few more bugs than Pens and Cephs

What bugs do carbapenems still not touch?

MRSA/E, enterococci, atypicals, pseudomonas

Characteristics of Carbapenems that make them good

increased penetration, higher affinity for PBPs, resistance to inactivation by BLs

What bugs produce carbapenemases that can inhibit carbapenems

pseudomonas, acinetobacter, enterobacteriaceae

What is the only BLI that has antimicrobial activity and against what bug?

Sulbactam, acinetobacter

ADRs of carbapenems

GI effects, ertapenem is associated with altered mental status

MOA of Vancomycin

targets petidoglycan to inhibit cell wall synthesis

Mechanism of resistance for vancomycin

binding site tail on peptidoglycan changed form Ala-Ala to Ala-Lac

What bugs can Vancomycin kill?

Gram positive bugs, including MRSA and PRSP; Does NOT kill Gm neg bugs

ADME of vancomycin

oral vanc is not absorbed, widely distributed, renally cleared

Vancomycin ADRs

Red man syndrome, pruritis, flushing, hypotension

Vancins MOA

Same as vanc plus has long tails that penetrate into plamsa membrane to disrupt it

What bugs do vancins kill?

Most gram positive bugs

MOA of Aminoglycosides

inhibits protein synthesis by binding at the 30s subunit of ribosome

Resistance mechanisms for AGs

limited penetration, enzymatic breakdown, mutation to ribosomes

Bugs that produce enzymes to breakdown AGs

enterococci, some enterobacteriaceae, Pseudomonas

Bugs that AGs kill

many gram negatives, including pseudomonas, gentamicin good against most susceptible Gram positives

ADRs of AGs

renal failure

Linezolid MOA

inhibits ribosomes at initiation of protein synthesis by binding to 23s rRNA of 50s subunit

Spectrum of Linezolid

All gram positive bugs

Big advantage of linezolid

can use exact same dose transitioning from IV to PO

Linezolid ADRs

GI, headache, Bone marrow suppression with long-term therapy, serotonin syndrome with SSRIs

Polymyxins MOA

disrupts outer membrane of Gram negative cells, meaning it kills only gram negative bugs

What are polymyxins good for?

Pseudomonas and acinetobacter when resistant to everything else

Why are polymyxins last resort

can be toxic to human cells and have a lot of side effects

Uncomplicated UTI definition

any infection confined to bladder with associated signs and symptoms

Complicated UTI definition

any infection in the GU tract that is beyond the bladder usually with systemic s/sx and fever

Primary pathogens responsible for acute cystitis and pyelonephritis

E. coli, Klebsiella, Proteus, other Gm negs

RFs for UTIs

female, sexual intercourse, untreated/inappropriately treated acute cystitis

Presentation of pyelonephritis

typical UTI S/Sx plus Fever, chills, flank pain, N/V, and altered mental status

Antimicrobials used for Pyelonephritis

Bactrim, FQs, Pip/tazo, Ceftriaxone and other CSPs, CPs, Aminoglycosides

Which treatments for pyelonephritis are usually reserved for more resistant bugs?

AGs and CPs

Patients with pyelonephritis need to be hospitalized if?

unstable vitals, dehydration, altered mental status

Do we always obtain urine culture in pyelonephritis?

YES

3 categories for patients for pyelonephritis

w/o sepsis oral therapy, w/o sepsis IV therapy, with sepsis

Sepsis and what it usually presents as

A condition where organ dysfunction can occur because of dysregulated infection response; usually presents with tachycardia, hypotension, and profound inflammation

Criteria for Septic shock

Persistent hypotension requiring pressors to maintain MAP >65, serum lactate greater than 2 mmol/L

Therapy for pyelonephritis w/o sepsis and oral drug

FQs, Bactrim, Amox/Clav, CSPs

Therapy for pyelonephritis w/o sepsis and IV drug

TGCs, 4GCs, Pip/tazo, FQs, CPs, Cefiderocol, Plazomycin, Older AGs

Therapy for pyelonephritis with sepsis

TGCs, 4GCs, Pip/tazo, FQs, CPs, Novel BL/BLIs, Cefiderocol, Plazomycin, Older AGs

4 step approach for choosing therapy in pyleonephritis

Assess Severity of illness, RFs for resistance, Patient specific considerations, Consider antibiogram (if septic only)

Duration of therapy for pyelonephritis

Effictive therapy for 5-7 days if on FQ, 7 days if on non-FQ

Pathogens responsible for CAUTIs

Staph, enterococcus, Pseudomonas, other typical UTI bugs

S/Sx of CAUTIs

altered mental status, purulent discharge (staph most likely), Systemic S/Sx

Diagnosis criteria for CAUTIs

> 1000 cfu/mL of 1 species plus Sx OR > 100,000 cfu/mL

RFs for prostatitis

sexual activity, urinary instrumentation, older than 65

Treatment for prostatitis

FQs and Bactrim

Length of treatment for acute prostatitis

2 weeks

Length of treatment for chronic prostatitis

6-12 weeks

Main pathogen for Purulent SSTIs

S. aureus (MSSA/MRSA)

Mild classification of SSTIs

localized infection with no systemic symptoms

Moderate classifications of SSTIs

few systemic symptoms, patient overall is stable

Severe classification of SSTIs

failed I&D and ABX, fever, tachycardia, tachypnea, WBC >12,000, clinically unstable

Treatment of mild Purulent SSTIs

I&D only

Empiric Treatment of Moderate Purulent SSTIs

Oral treatment with Bactrim, Doxycycline, or Clindamycin (alt)

Empiric Treatment of Severe Purulent SSTIs

IV: Vancomycin, Daptomycin, Linezolid, Ceftaroline, Vancins, Clinda if resistance less than 10-15%

Treatment of Purulent SSTI if MSSA

Cephalexin, Dicloxacillin, Amox/Clav

Do we use I&D for all Purulent SSTIs?

Yes

Treatment of Purulent SSTI if MRSA

Bactrim, Doxycycline, Clindamycin (alt), Linezolid

Duration of therapy for Purulent SSTIs

5-10 days outpatient, 7-10 days inpatient

Main pathogen for Non-purulent SSTIs

S. pyogenes

Empiric Treatment for Mild Non-purulent SSTIs

Oral: Pen VK, Cephalexin, Dicloxacillin, Clindamycin (Alt)

Empiric Treatment for Moderate Non-purulent SSTIs

IV: PenG, Cefazolin, Clindamycin, Ceftriaxone

Empiric Treatment for Severe Non-purulent SSTIs

IV: Vanc+Pip/tazo, Vanc+imipenem/cilastatin, Vanc+meropenem

Length of therapy for Non-purulent SSTIs

at least 5 days

Pathogens that cause necrotizing fasciitis

S. pyogenes, MRSA/MSSA, Vibrio, Aeromonas

RF for necrotizing fasciitis

DM, immunocompromised, venous insufficiency, ulcerations

Treatment for necrotizing fasciitis

surgical excision plus ABX

Empiric ABX choices for necrotizing fasciitis

Vanc, Dapto, linezolid PLUS Pip/tazo, CPs, Ceftriaxone or FQ plus metronidazole PLUS Clindamycin to suppress strep toxin

Treatment for necrotizing fasciitis if S. pyogenes

Penicillin plus Clindamycin

Treatment for necrotizing fasciitis if Vibrio

Doxy plus TGC

Treatment for necrotizing fasciitis if Aeromonas

Doxy plus Cipro or Ceftriaxone