Infectious Disease Topics · bacteria, decreasing sensitivity of dihdropteroate, prediction of...
Transcript of Infectious Disease Topics · bacteria, decreasing sensitivity of dihdropteroate, prediction of...
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Infectious Disease Topics:
pharmacology/antibiotic choices, disease and illness, supporting data, diagnosis,
outcomes.Frank Kaydo MSN, RN, ACNS-BC
Antibiotics
Antibiotics classes
Mechanism of action and resistance
Pharmacokinetics
Pharmacodynamics
Dosing
Adverse reactions/contraindications
Outcomes
Antibiotic Classes To Discuss
Beta Lactams
Penicillin, ex. PCN G, Amoxicillin
Cephalosporin's, ex. Cephalexin
Carbepenems, ex. Etrapenem
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Antibiotics Classes To Discuss
Fluoroquinolones
EX:
Ciprofloxacin
Levofloxacin
Moxifloxacin
Antibiotics Classes To Discuss
Macrolides
EX:
Erythromycin
Clarithromycin
Azithromycin
Antibiotics Classes To Discuss
Tetracycline
EX:
Doxycycline
Tetracycline
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Antibiotics Classes To Discuss
Glycopeptides
EX:
Vancomycin
Dalbavancin
Antibiotics Classes To Discuss
Lipopeptide
EX:
Daptomycin
Antibiotics Classes To Discuss
Anti-folate, sulfa
EX:
Trimethoprim
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Antibiotics Classes To Discuss
Aminoglycosides
EX:
Amikacin
Gentamycin
Tobramycin
Factors to consider
Antimicrobial Activity
Pharmacokinetics/Pharmacodynamics
Adverse Events
Resistance Potential
Cost
Clinical Studies
Availability in Hospital Formulary
Penicillin History
1928- Fleming used experiments involving the common staphylococcal bacteria.
A petri dish sitting by an open window was contaminated with mold spores-the bacteria in the dish close to mold were dying.
Mold was identified it as a member of the Penicillium genus.
Fleming published-discovery of penicillin in the British Journal of Experimental Pathology in 1929.
1940 - Howard Florey and Ernst Chain mass production WWII-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520913/
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Beta Lactam AntibioticsB-lactams
A class of broad-spectrum antibiotics, consisting of all antibiotic agents that contain a beta-lactam ring as part of the molecular structures.
Four member lactam ring Nitrogen attached to B-carbon
As mentioned –penicillin and derivatives, cephalosporin, carbapenems and monbactams.
Beta Lactam Ring
https://www.google.com/search?q=beta+lactam+ring&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjMov_78PnVAhVHxCYKHaMRCoQQ_AUICigB&biw=1920&bih=964#imgrc=JB5EgUHR3yX_aM:
Beta Lactam Antibiotics-penicillin
Penicillin, ex. PCN G, PCN VK, IV or PO
MOA- inhibition of bacterial peptoglycan wall by blocking PCN binding protein. Inhibit bacterial cell wall biosynthesis. Bactericidal, Kills bacteria.
Pharmacodynamics/Pharmacokinetics,
Renal excreted, dosing time dependent, concentration to be above MIC 60% of the TIME
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Penicillin
Dosing and monitoring the drug Ex. PCN VK.500 mg PO Q 6hrs x14 days. Ex. PCN G, 3 million units IV,IMCob/diff, cmp, sed, crp, absolute eosinophils Spectrum of activity Strep Pneum, Gm+ org, +TreponemaNo MSSA, MRSA, Enterococcus, No Gm -.PCN G will cover syphilis ADR, Jarisch – Herxheimer, serum sickness,
Hemolytic anemia.
Nafcillin
MOA- inhibition of bacterial peptoglycan wall by blocking PCN binding protein. Inhibit bacterial cell wall biosynthesis. Bactericidal, Kills bacteria.
Pharmacodynamics/Pharmacokinetics,
Biliary excreted, dosing time dependent, concentration to be above MIC 60% of the TIME
Nafcillin
Dosing and monitoring the drug
Ex. Nafcillin 2 gram IV Q 4hrs x 14 days
Cob/diff, cmp, sed, crp, absolute eosinophils
Spectrum of activity
MSSA Only
ADR, neutropenia, elevated serum sodium if given IV infusion.
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Resistance to Penicillin
Bacteria form beta lactamase through hydrolysis. This breaks or destroys the B-Lactam ring. The drug will not attach.
Cephalosporin- Beta Lactams
Subclass of β-lactam antibiotics. Derived from Acremonium - fungus, also known as Cephalosporium.
Cephalosporin's were discovered in 1945. market sale 1960s.
Generations 1-5+ First-generation cephalosporin are active against Gram-positive bacteria and following generations have increasing activity against Gram-negative bacteria.
Cephalosporin- Beta Lactams
https://www.google.com/search?q=cephalosporins&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjy5JDGgfrVAhUi4oMKHQ1cAtMQ_AUICygC&biw=1920&bih=964#imgrc=tEORlUNq3jW5iM:
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Cephalosporin- Beta Lactams
Drug: Cefazolin, Cephalexin, Cefoxitin, Ceftriaxone, Cefdinir, Cefepime
MOA- inhibits peptidoglycan synthesis by interfering with PCN Binding Protein PCB.
Pharmacodynamics/Pharmacokinetics,
Renal excreted. Adjust renal with GFR <25-50%
Cephalosporin- Beta Lactams
Dosing and monitoring the drug
1st generation
Ex. Cephalexin 250-750 mg Po Q 6hrs x 14 days.
Renal dose adjustment needed if GFR <50ml/min
Cbc/diff/cmp/sed crp
Ex. Cephazolin 1-2 gram IV Q8 hrs x 14 days.
Renal dose adjustment needed if GFR <35ml/min
Cbc/diff/cmp/sed crp
Cephalosporin- Beta Lactams
Spectrum of activity
MSSA, all strep and Gm + cocci, Ecoli, Klebseila.
No anaerobes, no atypicals, no enterococcus.
ADR
Drug rash, fever, GI intolerance
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Cephalosporin- Beta Lactams
Dosing and monitoring the drug
2nd generation
Ex. Cefoxitin 1-2 gram IV Q24 hrs x 14 days.
Renal excreted. Watch cbc/diff cmp
Spectrum of activity
MSSA and all strep as prev, Ecoli – Klebseilla, + anaerobes, No atpycials.
ADR
Any allergy, GI intolerance
Cephalosporin- Beta Lactams
Dosing and monitoring the drug 3 rd generation Ex. Cefdinir 300mg PO Q 12 hrs x 14 days.Renal excretion and dose, esp HD. Give after Hemodialysis on those days. Ex. Ceftriaxone 1-2 gram IV Q 12-24 hrs x 14
days.Hepatic excretion – biliary excretion
Cbc/diff, cmp, sed, crp
Cephalosporin- Beta Lactams
Spectrum of activity
Extended gram negative coverage than previous, MSSA, all streptococci, Tier 1-4 gram -. Ecoli – citrobacter. No anaerobes, no atypicals. CSF coverage
ADR
Any allergy, GI intolerance
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Cephalosporin- Beta Lactams
Dosing and monitoring the drug
4th generation Ex. Cefepime 1-2 gram IV Q 8-12 hrs x 14 days
Renal excretion and dose adjusted to GFR, esp HD. Give after Hemodialysis on those days.
Spectrum of activityMSSA, all strep, pseudomonas, Gm negatives as prev, No anaerobes, no atypicals. Penetrates CSF ADR
Any allergy, GI intolerance
Cephalosporin- Beta Lactams
Resistance on strains of Ecoli and Klebsiella expressing beta lactamases can hydrolyze most cephalosporin
Carbepenem – Beta Lactams
Class of beta lactam antibiotics. To kill bacteria they again bind -penicillin-binding proteins and inhibit cell wall synthesis. Used as broader spectrum of activity compared to previous cephalosporin's and penicillin's.
Produced first from S. clavuligerus and Streptomyces cattleya.
Development in the 1960’s and 70’s due to the need for a beta lactamase inhibitor. (beta lactamase is produced by bacteria to disrupt the beta ring and render the antibiotic useless).
Infections known or suspected to be caused by multidrug-resistant (MDR) bacteria
Ertapenem, Imipenem, meropenem, Doripenem – IV infusions
Carbon atom at the C-1 position was found to play a major role in the potency and spectrum of carbapenems and in their stability against β-lactamases
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Carbepenem – Beta Lactams
Drug names: Ertapenem, Imipenem, meropenem, Doripenem – IV.
Mechanism of Action: Inhibits trans peptidoglycan synthesis by interfering with Penicillin Binding Protein ( PBP ). Again as others a bactericidal drug.
Pharmacodynamics/Pharmacokinetics, Renal excreted. Adjust renal with GFR.
only need to be above MIC 40% of time to be effective.
Carbepenem – Beta Lactams
Dosing and monitoring the drug
Ex. Ertapenem 500mg to 1 gram IV Q 24-48hrs x 14days IV
Ex. Meropenem 250mg -1 gram IV Q 8,12 hrs IV.
Cbc/diff, cmp. Sed, crp
Spectrum of activity
MSSA, all strep, Tier 1-4 anaerobes, + ESBL bacteria, gm neg,
Meropenem will cover pseudomonas.
ADR Any allergy, GI intolerance, seizures in Ertapenem, cdiff, eosinophilia, neut
Quinolone Antibiotics
Ciprofloxacin, Levofloxacin, Moxifloxacin
Development: large group of broad-spectrum bactericides. Most widely used group is the fluoroquinolones. There is a fluorine atom in their chemical structure making them effective Gram- and Gram+.
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Fluoroquinolones
Mechanism of action: Inhibits DNA gyrase topoisomerase 2 and 4, inhibiting DNA replication and transcription. Blocking topoisomerase 2 prevents relaxation of cell DNA, blocks separation of replicated chromosomal DNA during cell division. Bactericidal.
Post antibiotic effect.
Pharmacodynamics/Pharmacokinetics,
2/3 drug excreted renal and 1/3 Hepatic, they are concentration based
Fluoroquinolones
Dosing and monitoring the drug
Ex. Ciprofloxacin 250-750 mg Po, IV Q 8-12-24 hrs x 14 days
Ex. Levofloxacin 250-750 mg PO,IV Q 12-24 hrs x 14 days.
Ex. Moxifloxacin 400 mg PO Q 24 hrs x 14 days.
Most extensively used for bacterial infections as it distributes well. Excellent bioavailability.
As the Generation go from 1-4, Gram neg coverage expands to Gram + coverage to broad spectrum coverage. Absorption impaired by Ca, Mg, iron, Al. take 2 hrs before o 4 hrs after.
QT, Inr with medications,
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Fluoroquinolones
https://www.google.com/search?q=fluoroquinolone+generations&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjTsMj55v7VAhUBcyYKHdqNDwwQ_AUICigB&biw=1920&bih=964#imgrc=IBwwHvOSDlXsxM:
Fluoroquinolones
Spectrum of activity: strep (dependent on drug), staph (dependent on drug), enterococcus in urine, Ecoli-pseudomonas, Acinetobacter, ESBL organisms, Anaerobes (Moxi), + atypical such as Moraxella caterlais, H. Influenzae, H.Pylori
ADR: previous allergy, QTc prolongation, tendonitis, other opportunistic infections, do not use in children or pregnancy DT cartilage damage
Macrolides
Drugs – Erythromycin, Clarithromycin, Azithromycin
Development – 1952,large macrocyclic lactone ring, macrocyclic lactone nucleus.
MOA – Inhibits RNA protein synthesis at chain elongation step. Binds to 50s.
Pharmacodynamics/Pharmacokinetics – bacterial static/cidal, concentration dose dependent. PO or some IV , Ex.
Spectrum of activity + s.peumoniae, all atypicals ( ), NO staph, No gm neg, enterococcus , no anaerobes.
ADR – GI, hepatotoxicity, QTc prolongation.
Resistance – Drug efflux, ribosomal protection by enzymes, decreased rug binding, hydrolysis, chromosomal mutation that alter 50s.
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Macrolide Ring
https://www.google.com/search?q=macrolide+development&source=lnms&tbm=isch&sa=X&ved=0ahUKEwiM76LB1YvWAhVqxYMKHSUvDFAQ_AUICygC&biw=1920&bih=964#imgrc=3CLNJNisy1cD_M:
Tetracycline
Drugs – Tetracycline and Doxycycline
Development – 1940 for microbial infections.
MOA – binds to 30s ribosomal subunit of incoming tTNA, blocks, causes conformational changes to terminate protein synthesis.
Pharmacodynamics/Pharmacokinetics – bacteriostatic, mixed hepatic renal elimination and monitoring, concentration dependent.
Spectrum of activity ADR – most strep, all staph, some enterococcus, gm Ecoli to AB, NO beta hemolytic strep, pseudomonas, provientia, +atypicals.
Resistance – decreased accumulation of drug. Production of ribosomal protection proteins that’s displaces it form the target, enzymatic inactivation.
Glycopeptide
Drugs – Vancomycin IV, PO. Telavancin IV
Development – in the 1950s due to PCN resistance
MOA – vanco, Binds D ala preventing cross linking of peptidoglycan. Blocks binding to tran-glycoytates. Telav – inhibits cell wall synthesis, disrupts bacterial cell membrane.
Pharmacodynamics/Pharmacokinetics - IV Vanc is bactericidal, time dependent with peak and trough, renal adjustment. Telav – is bactericidal, concentration dependent, renal adjustment. No peak or trough.
vancomycin 10-20mg/kg/IV x1 first load dose then adjust based on creat, GFR, wt, trough 30
min prior to dose 3. twice weekly labs and weekly trough.
Spectrum of activity – IV Vanc + MRSA, all staph, strep, enterococcus. Gram +. Telav + same as Vanc also includes Gram + anaerobes.
ADR – Vanco IV, redman syndrome, nephrotoxicity, ototoxicity. Telav, Prolonged QTc, nephrotoxicity.
Resistance – at the binding site, D ala is replaced by D lacate
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Lipopeptide
Drugs – Daptomycin - IV, Cubacin
Development – 50 yr old drug, popular 1980-1900, Cubist marketed 1997. product found in soil, Actinomycte, Streptomyces.
MOA – Ca dependent insertion of lipid tail into membrane which leads to depoloration with K+ efflux arrest of DNA, RNA and protein synthesis and rapid cell death (not lysis). No cell wall disruption.
Pharmacodynamics/Pharmacokinetics - bactericidal, concentration dependent at 4-6mg/kg/Q24-48 hrs IV or post HD.---renal dose
Spectrum of activity – vancomycin resistant strains, strep, MRSA, MSSA, enterococcus
poor cns distribution, poor lung distribution
ADR – myopathy, rhabdomyolysis, pneumonitis, nephrotoxicity
Resistance – not known
Anti –Folate Agents
Drugs - sulfamethoxazole – trimethoprim ( Bactrim SS or DS). IV or PO. 5:1, 800/160mg
ex Bactrim DS
Development – 1960’s antibacterial
MOA – sulfamethoxazole, inhibits bacterial folic acid synthesis (dihydro-pteroate).
trimethoprim, antimetabolite of folic acid, inhibit (dihydrofolate reductase)
Pharmacodynamics/Pharmacokinetics – in combination is bactericidal. Renal adjusted. Mixed hepatic and renal excretion
Spectrum of activity – MRSA, not well against strep, B.capacia, S.maltophilis, Y.enterocolitica, F. tularenis, P carini.
+drug of choice for Listeria, pneumocystis pneumoniae, Nocardia.
ADR –SJS, hypersensitivity, GI, nephrotoxicity, anemia, bone marrow sup, hyper K+, increased INR, neonatal jaundice, increased bilirubin,
Resistance – due to decreased accumulation, increased PABA production n bacteria, decreasing sensitivity of dihdropteroate, prediction of dihydrofolate reductase
Aminoglycosides
Drugs – Amikacin IV,IM, Neb. Gentamycin IV, IM. Tobramycin IV,IM Neb.
Ex Amikacin 5-7 m/kg/q8hrs, Gentamycin 2-3 mg/kg/qh8hr or synergistic dose 1 mg/kg,
Development – mainly useful against gram negative bacteria
MOA – interferes with protein synthesis by binding to 30s and 50s ribosomal subunits, (static), blocks translocation , depolarizes the cell membrane – porin that needs O2 (cidal) and also prevents DNA replication.
Pharmacodynamic/Pharmacokinetics – Bacterial static/cidal, renal adjusted, concentration dependent. Post antibiotic effect, poorly absorbed through GI, + synergy with beta lactam on cell wall
Spectrum of activity – gram negative organisms, includes pseudomonas. Mycobacterium. Some strep and staph coverage.
ADR – ototoxicity, renal failure – nephrotoxicity.
Resistance – by adenylylation, acetylation, phosphorylation. Impaired cell entry. Mutation of receptor proteins.
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I. Urinary Tract Infection
How to DX: asymptomatic bacteriuria vs bacterial infection
Asymptomatic bacteriuria -the presence of bacteria in UA/C&S, without clinical evidence of infection such as fever, dysuria, or radiology.
Differential – Volovaginitis, anatomical change, urethritis, HSV, viral, sexual activity. Etc.. Not recommended treat
UTI – acute uncomplicated cystitis, IDSA - presence of urinary symptoms including dysuria frequency or urgency in the setting of bacterial presence.
UA – leukocyte esterase, nitrates, bacteria, WBC
C&S - >100,000 colony count HPF, as low as 1,000 col per HPF
Urinary Tract Infection
Bacteriuria may be as high as 25-50% in institutionalized women and 15-35% and institutionalized man.
In regards to women and cystitis it is almost always an ascending infection. Colonization of the periurethral area precedes this infectious process.
In regards to men, urinary tract infections are especially rare in young men. Also lack of circumcision increases risk of colonization. Homosexual and heterosexual practices increased risks.
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Urinary Tract Infection
Pathogens: mainly women
Escherichia coli accounts for 80%
Staphylococcus saprophyticus 5-15%.
Staphylococcus species.
Klebsiella species
Proteus species
Men, including the above +
50% cases include Proteus, providencia, Klebsiella, multiple gram-negative enteric, enterococcus
Urinary Tract Infection
Elderly - much higher incidence of anatomic abnormalities including benign prostatic hypertrophy, urethral stricture, neurogenic bladder.
Clinical manifestations between women/men are generally the same including dysuria, urgency, frequency, fatigue, nausea and lethargy.
Common terminology:
Uncomplicated cystitis – Bladder infection
Complicated cystitis – Bladder infection with syndrome ( )
Prostatitis – infected prostate
Acute pyelonephritis- ascending infection to the renal parenchyma.
Urinary Tract Infection
Treatments:
Uncomplicated cystitis, 3-7 days, Sulfa, nitrofurantoin, cephalosporin, ciprofloxacin.
Complicated cystitis, 10-14 days, PO – IV, depends on bacteria.
Prostatitis, Acute case 2-4 weeks bacteria specific. Chronic 3-6 weeks. sulfa, fluoroquinolone, cephalosporin.
Acute pyelonephritis, 14 days, bacteria specific treatment.
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Urinary Tract Infection
Catheter related: Foley, suprapubic.
Predisposes patients for several reasons including conduit for bacteria to travel, biofilm, inadequate emptying, reservoir, manipulation and trauma.
3 - 10% chance per day of developing bacteriuria.
Escherichia coli and 25% of the cases. + previous.
Urinary Tract Infection
Sample medications
Bactrim DS one tab twice daily
Macrobid 100 mg twice daily
Fosfomycin 13 g dose
Cipro 250 mg-500 mg twice daily
Beta-lactam
Next Section
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MRSA - Skin
Methicillin Resistant Staphylococcus Aureus.
Mortality/morbidity significant
Pre – antibiotic era, 80% blood stream infections
MRSA 30% mortality with ATB, high avg 65%
CDC = 1999- 2000
125,969 hospitalizations, MRSA infections
31,440 blood stream infections
29,823 pneumonia
Recent data
MRSA causes approx 19,000 deaths per year
( > HIV, viral Hep, TB, Influenza )
evolving pathogens CID 2014 . 58 ( )
MRSA - Skin
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MRSA 2004-2013St E
15% probably related to CA‐MRSA
MRSA - skin
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Strep
Cellulitis -MRSAoutpatient scenario, non animal bite Impetigo
Secondary infected skin lesion ( eczema, ulcers, laceration ).
Mupirocin 2%
Cutaneous abscess/boils
I&D alone
Add ATB if – extensive numerous sites, rapid progression, hand, face genital, phlebitis . ATB choices – Clinda, Doxy, TMX, Linezolid
Beta hemolytic strep seen less frequently
Clindamycin alone or with sulfa
Doxy and beta lactam
Linezolid alone
Hygiene
Table – oral agents for CA- MRSA
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Parenteral Agents for MRSA
Ceftaroline 600 my IV Q 12hrs
Vancomycin 15-25 mg/kg ( 1 gram ? ) IV Q 12hrs
Daptomycin 4mg/kg Q 12hrs – cellulitis
6mg/kg ( 8mg/kg ) for bacteremia and
endocarditis
Linezolid 600 mg IV Q 12hrs – also PO is 100% bioavailable
Tigecycline 100 mg X1, then 50 MG Q 12 hrs
cid 2008: 46
Next Section
Community Acquired PneumoniaCAP
Defined - as an acute infection of the lower respiratory parenchyma obtain by person not hospitalized or living in a long term care facility.
Diagnosed –
Chest x-ray Microbiologic studies
Clinical evaluation.
Differential – CHF, septic emboli, malignancy, for body, other agent
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CAP
2-3 million
2-3 million cases CAP
10 million PCP visits
500,000 hospitalizations
45,000 deaths in US
Mortality 2-30% in hospital
< 2% non hospitalized pt
CAP
Most common causes
Strep pneumoniae
Haemophilus influenza, Moraxella catarrhalis
Atypical causes
Chlamydia pneumoniae Mycoplasma pneumoniae
Legionella
Staphylococcus, Klebsiella, anaerobes, nocardia, fungal.
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CAP
S. Pneumoniae is most common etiologic agent.
2/3 bacteremia pneumonia
Most frequent cause of lethal CAP
Management complicated by evolution of multi Drug resistance.
Beta lactam generally drug of choice but resistant strain
mic > 2 ug/ml will have poor response.
Macrolide, Doxy, cefuroxime are good vs Pen susceptible.
Strains are less predictable with strain reduced PEN susceptibility
(mic .1-1.0)
Vanco for resistant strep pneumo
Levofloxacin for mic 1.0 – 2.0 vs Moxi mic 0.12 – 0.25
CAP therapy 1986
1986 CAP –
Discussed changing focus from X ray appearance to etiologic agent-
Hosp acquired Pneumonia was defined.
Focus CAP - Strep pneumoniae
- Mycoplasma
VIP DD ---- Pen choice
Classic DD – History and phys exam = Imperative.
-Lab
- Gram stain sputum cx
Therapy :
Strep pneumo -------- Pen G or PO, allergy – E-Mycin
Mycoplasma, E-Mycin or tetracycline
--------- if you cant tell, E-Mycin
H. Influ = Amp or Cefuroxime , Doxy
Kleb – Cefazolin
Aspiration, Pen or Clinda
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Outpatient CAP
Macrolide or Doxycycline
With Comorbidities :Chronic heart, lung, liver, kidney, DM, ETOH,
asplenia, IC, daily ATB within 3 mo.
** increase %Respiratory Fluoroquinolones or *Beta lactam + macrolide or Doxy
* Amoxil HD, AM/CL, 3rd gen oral Ceph (Cefdinir), etc..
Next Section
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Clostridium DifficileC-DIFF
Clostridium Difficile
Spore-forming, anaerobic, gram-positive bacterium
• Causes gastrointestinal infections resulting in diarrhea and colitis
Severity ranges from mild colitis to toxic megacolon and death
• Leading cause of healthcare-associated infectious diarrhea in US
Cost
Leading cause of nosocomial infection
Steadily increasing over last decade
Estimated 500,000 new cases per year
15,000 – 20,000 associated deaths
Annual cost exceeding $1billion dollars
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Risk factors
Classic risk factors:
Antibiotic therapy
Advanced age
Prolonged stay in healthcare facility
High severity of illness
Additional risk factors
Inflammatory bowel disease
Gastrointestinal surgery
Gastric acid suppression (PPIs)
Immunosuppression
Testing for
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Test Advantage(s) Disadvantage(s)
Toxin testing
Enzymeimmunoassay
Rapid, simple, inexpensive
Least sensitive method, some detect only toxin A (some strains only produce toxin B)
Tissue culture cytotoxicity
Organism identification
More sensitive than enzyme immunoassay
Labor intensive; requires 24–48 hours for a final result, special equipment; not as sensitive as generally thought
Detection of glutamate dehydrogenase
Rapid, sensitive, may prove useful as a triage or screening tool
Not specific, toxin testing required to verify diagnosis; may not be 100% sensitive
PCR Rapid, sensitive, detects presence of toxin gene
Cost, special equipment, may be “too” sensitive
Stool culture Most sensitive test available when performed appropriately
May be associated with false-positive results if isolate is not tested for toxin; labor-intensive; requires 48–96 hours for results
Testing
Testing for C. difficile or its toxins should be performed only on unformed stool (unless ileus is suspected)
Testing asymptomatic patients not clinically useful and not recommended outside of epidemiological studies
Stool culture with confirmation of isolate toxigenicity (“toxigenic culture”) provides the standard against which other clinical test results should be compared
Steps for testing
EIA considered a suboptimal alternative approach for diagnosis
2-step testing can help to overcome low sensitivity of toxin testing; this approach remains an interim recommendation
More data on the utility of PCR testing is necessary before it can be recommended for routine testing
Repeat testing during same episode of diarrhea is discouraged
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Principles
• Discontinue offending antimicrobial agent (if possible)
Send stool specimen for C. difficile testingnitiate CDI therapy either empirically or following confirmation of diagnosis (depending on clinical urgency)
Pharmacotherapy PO Vancomycin
Metronidazole ( not FDA approved )
Other, New – Dificid 200 mg po daily x 10days
Supportive treatment
• Monitor for symptom resolution and be aware of recurrence after treatment discontinuation
Treatment
• General principles
– Whenever possible withdraw the offending antibiotic
– Use oral antimicrobials whenever possible– Be patient- some improvement seen in
first 2 days but mean time until resolution of diarrhea is 2-4 days. Don’t call them nonresponders until 6 days of therapy
– Treat for 10 days– Avoid antiperistalsis agents
Severity
Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31(5):431‐455.
Clinical scenario Supportive clinical data Recommended treatment
Mild to moderate Leukocytosis (WBC < 15,000 cells/uL) or SCr level < 1.5 times premorbid level
Metronidazole 500 mg 3 times per day PO for 10-14 days
Severe Leukocytosis (WBC ≥ 15,000 cells/uL) or SCr level ≥ 1.5 times premorbid level
Vancomycin 125 mg 4 times per day PO for 10-14 days
Severe, complicated
Hypotension or shock, ileus, megacolon
Vancomycin 500 mg 4 times per day PO or by nasogastric tube plus metronidazole 500 mg IV q 8 hrs
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Treatment drugs
• Oral metronidazole: 250 mg qid or 500 mg TID for 10 days; low cost, effective ( poor outcomes )
• Oral Vancomycin: 125-250 mg QID for 10 days
High cost, if reoccurrence will taper dose.
New treatment step ---fidaxomicin
Flagyl
MIC 90 of 0.4 ug/ml vs. C. difficile
98% cure rate documented
Well absorbed in the upper GI tract: in healthy volunteers fecal concentration of drug low to undetectable
Bactericidal fecal concentrations achieved in the stool of patients with CDAD: fecal concentrations decrease as diarrhea improves Drug secreted directly across inflamed mucosa
Decreased intestinal transit time with diarrhea decreases absorption
PO Vancomycin
• MIC 90 of 1.6 ug/ml
• Fecal concentrations of 2,000 to 5,000 ug/ml with po drug
• Cure rates 98-100%
• Concerns of selecting for vancomycin resistant Enterococcus (VRE)
• IV doesn’t work, only PO
• Can be given by enema
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Recurrent C- Diff
CDI recurrence is a significant challenge
Rates of recurrent CDI:
20% after first episode
45% after first recurrence
65% after two or more recurrences
New trends
Fidaxomicin – recently approved by FDA in 2011 –monocyclic antibiotic –bactericidal against c. diff
Dificid -
Pro Biotics – Kefir, Florastor, Lactobacillus,acidophilus
Next Section
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Lyme Disease
Lyme Disease
Most common tick borne illness in North America and Europe – 90% of US cases – Massachusetts, NY, NJ, Connecticut, RI, PA, Minnesota, Wisconsin, and CA
Peak season May-September
Causative agent – spirochete Borrelia burgdorferi. Transmitted by Ixodes ticks – scapularis and pacificus
>20% of Ixodes ticks in prevalent areas may be infected
Prevention
Protective clothing and tick repellant sprays
Check frequently for ticks and early removal. Removal recommended with tweezers – do not twist
Routine prophylaxis generally not indicated – only in area of known prevalence with tick in place >36 hrs, proven Ixodes tick, prophylaxis administered with 72 hrs of tick removal. Prophylaxis consists of doxycycline 200 mg po x1
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Diagnosis
Early (3-32 days post-bite)– fever/chills, H/A, myalgias, erythema migrans. Ring-like rash which spreads outward, often with central clearing. Occurs 75% of cases
Cardiac involvement (5 wks-7 mos post-bite) -Sx chest pain, syncope, dyspnea. May develop heart block and/or myocarditis
Neurological involvement (5 wks-7 mos post-bite) Sx severe or prolonged headache, nuchal rigidity, cranial nerve palsy, peripheral neuropathy, Bell’s palsy. Should get an LP if meningeal Sx. CSF may show lymphocytic pleocytosis
Diagnosis
Stage III (late) Joint involvement - May begin several days after rash up to 2 years later
Usually affects large joints – knees, hips
Pts may or may not have h/o tick bite – may occur without their knowledge. Assess risk – hunter, lot of time outdoors, etc
Lab Testing
None of the testing is definitive – should only be used to confirm
Lyme by EIA or IFA – early testing
Lyme IgG and IgM by Western Blot (40-60% sensitivity)
Lyme disease Ab by Western Blot – usu. Considered confirmation testing, not sensitive in early disease
May consider testing by PCR on CSF cx
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CDC Recommendation
Treatment
Depends on the stage of the infection
Early Lyme, erythema migrans: expanding erythema from the site of the bite. No neurologic issues, tx with po:
Doxycycline 100 mg po bid x10-21 days
Or amoxicillin 500 mg po tid x14-21 days
Or cefuroxime 500 mg po bid x14-21 days
Macrolides are less effective and only to be used if above atb are contraindicated
Treatment in later stages
Neurological effects – meningitis or radiculopathy, cranial nerve involvement
First line is IV ceftriaxone 2 Gm IV qday for 14-28 days
Or Cefotaxime 2 Gms q8h IV
Or PCN G 3-4 million units q4h
May use oral doxycycline (high bioavailability with po) at higher doses for 14-28 days if beta-lactams contraindicated
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Treatment
Cardiac involvement – start of therapy IV, may change to po to complete. 14-21 days
Joint involvement – may consider IV or po. Tx for 4 wks. May need 2nd 4 wk course if Sx do not resolve or reoccur.
The future of Antibiotics
Cost to develop
Cost to patient
Need due to resistance
New medications