Infectious Disease Topics · bacteria, decreasing sensitivity of dihdropteroate, prediction of dihydrofolate reductase Aminoglycosides

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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


Macrolides

EX:

Erythromycin

Clarithromycin

Azithromycin


Tetracycline

EX:

Doxycycline

Tetracycline

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Glycopeptides

EX:

Vancomycin

Dalbavancin


Lipopeptide

EX:

Daptomycin


Anti-folate, sulfa

EX:

Trimethoprim

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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.


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.


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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Drug: Cefazolin, Cephalexin, Cefoxitin, Ceftriaxone, Cefdinir, Cefepime

MOA- inhibits peptidoglycan synthesis by interfering with PCN Binding Protein PCB.


Renal excreted. Adjust renal with GFR <25-50%



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



MSSA, all strep and Gm + cocci, Ecoli, Klebseila.

No anaerobes, no atypicals, no enterococcus.

ADR

Drug rash, fever, GI intolerance

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2nd generation

Ex. Cefoxitin 1-2 gram IV Q24 hrs x 14 days.

Renal excreted. Watch cbc/diff cmp


MSSA and all strep as prev, Ecoli – Klebseilla, + anaerobes, No atpycials.

ADR

Any allergy, GI intolerance


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



Extended gram negative coverage than previous, MSSA, all streptococci, Tier 1-4 gram -. Ecoli – citrobacter. No anaerobes, no atypicals. CSF coverage

ADR


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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



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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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.



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


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.


2/3 drug excreted renal and 1/3 Hepatic, they are concentration based

Fluoroquinolones


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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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


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.


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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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.


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

10/2/2017

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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

Infectious Disease Topics · bacteria, decreasing sensitivity of dihdropteroate, prediction of dihydrofolate reductase Aminoglycosides

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