Antibiotic therapyAntibiotic therapy

Vaccines for healthcare workerVaccines for healthcare worker

Key pointsKey points

Introduction Choice of the proper antibioticAntimicrobial combinationsChoice of the route and efficacy assessment

Sir A. Fleming: discoverer of Penicillin

Noble prize 1945

AntibioticsAntibiotics

PCNsCephalosporinsCarbapenemMonobactamsGlycopeptideAminoglycosideFluroquinolone

PCNPCN

PCN G PCN V Amoxicillin Cloxacillin Oxacillin Ampicillin Piperacillin Methicillin

Choice of the proper agentChoice of the proper agent

1) Identification of the organism

2) Antimicrobial susceptibility

3) The narrowest effective spectrum

4) Host factors (Allergy, Age, renal and liver, site of infection, pregnancy, metabolic abnormalities)

Identification of the organismIdentification of the organismGram stain (CSF, Pleural, synovial,

peritoneal, urine, sputum)ELISA / latex agglutinationPCRCULTURE (best if before Abx)Bacteriologic statistics (the application of

knowledge of the organisms most likely to cause infection in a given clinical sitting)

Antimicrobial susceptibilityAntimicrobial susceptibility

Disk diffusion method Epsilometer (E-test) Minimum inhibitory conc. (MIC) Minimum bactercidal conc. (MBC) Specialized testing for: fastidious organisms

(obligate anaerobes), Haemophilus spp, pneumococci, MRSA

Resistance mechanism of the bacteria: eg: Staph. aureus, E. coli, Enterbacter …..

Pharmacodynamic profilePharmacodynamic profile

Area under the curve / time curve to MIC (AUC / MIC)

Maximal serum conc. / MIC (C max / MIC)Time during dosing interval that plasma

conc. exceed the MIC (t / MIC)

Conc. & Time dependent Conc. & Time dependent dosingdosing

Conc. dependent (FQ, Ag) increase in conc leads to a more rapid rate of bacterial death (i.e. large dose at long intervals)

Time dependent (-lactams, vancomycin) reduction in bacterial density is proportional to the time that the conc. exceeds MIC (i.e. sufficient dose at appropriate intervals to keep conc. above MIC)

Organism A

Organism B Organism C

Con

cent

rati

on

Time

A : resistant; B : moderately susceptible; C very susceptible

Resistance selectionResistance selection

Antibiotic X

Antibiotic X

days

Published dataPublished data

Manuals eg: Sanford’s Medical letter on drugs and therapeutics

(nb: use this information within its context)

Host factorsHost factors

Previous history of adverse reactionsNeutrophil function neutropenic are

treated aggressivelyCLL, Multiple Myeloma, asplenia

treated empirically

Age Age

Renal function (impaired physiologic function)

AbsorptionTetracyclinesINH hepatotoxicityNephrotoxicityAg and cochlear toxicity

Genetic / metabolic Genetic / metabolic

Hemolysis in G6PD deficiency DM : sulfa drugs can potentiate the

sulfonylurea hypoglycemic agents - Dextrose load - Poor IM absorption (use IV route)

PregnancyPregnancy Safe : PCN, cephalosporin, erythromycin Dangerous: tetracyclines (hepatic toxicity,

dental discoloration) ? metronidazoleFQ Contrindicated ?? rifampin, Ag, azithromyccin, clindamycin,

imipenem,vancomycin, TMP

Abx dose needs to be increased?

Renal and liver fxRenal and liver fx

Vancomycin & Aminoglycosides

Site of infectionSite of infectionOptimal therapy requires concentrations >

MIC at the site of infection Meningitis Endocarditis Osteomylitis Chronic prostatitis Intraocular infections Abscesses Foreign body UTI

Immune systemImmune system

Abx can cause immune suppression esp. in the immunosuppressed patients

Suppress monocyte transformation, phagocytosis, chemotaxis, antibody production

CombinationsCombinations

Some physicians use combinations for the sense of security deleterious effects

Indications: 1) prevention of emergence of resistant bacteria : TB, staph endocarditis

2) polymicrobial infections : abd. sepsis 3) initial therapy: eg: Ag + piperacillin4)Synergism:…

SynergismSynergism

For resistant organismsLimited data to support their benefite.g.: PCN + Ag Enterococcal endocarditisOxacillin + Ag Staph. endocarditis Anti-pseudomonal - lactam + Ag

Pseudomonas bacteremia Impaired host

AntagonismAntagonism

Too many in vitro reportsClinically was seen in : PCN + tetracyclines2 -lactams induce lactamasesMore important in immunosuppressed pts

Adverse effectsAdverse effects

5% of pts will have a side effectCombinations more cost, more adverse

effects

AnaphylaxisAnaphylaxisBeta lactams are the most common ABx to

cause anaphylaxisPCN risk of anaphylaxis: 0.01%Death occurs in 1 / 100,000 courses10 - 20% of pts who claim to have an allergy to

PCN are truly allergic50% of pts with a positive skin test: reaction

AnaphylaxisAnaphylaxis

PCN cross reaction with Cephalosporins Minimum cross reaction with carbapenem 1% No cross reaction with Aztreonam (except

ceftazidime)

Route Route

Oral stable , mild infection (reliable pts)IV serious infections (sepsis) + DM

Monitoring the responseMonitoring the response

ClinicallyDrug levelsLab tests

CostCost

If all other factors are equal, the least expensive drug should be chosen

Needle stick Needle stick

Risk of transmission

- Hepatitis B virus 30%- Hepatitis C virus 3%- HIV 0.3%

HBV VaccineHBV Vaccine recommendationsrecommendations

HB vaccine offered for all HCW– Required in US (1991)– Human rights issues (what if they refused ??)

Check response after 1 month– Responders: ….. 10 IU/l – Non responders………. < 10 IU/l

HBV vaccineHBV vaccine

Does not transmit the virus3 shots at 0, 1, 6 monthsThe series is administered once A booster shot can be given in times of

outbreak conditionsIf you are exposed to HBV immediate

vaccination is extremely helpful

HBV vaccine (cont)HBV vaccine (cont)

You do not need to accept the vaccine You can decline it and sign a declination form If you are exposed to HBV or changed your mind,

you can still receive it

Your employer might not offer you the vaccine if:– You are vaccinated– Have Antibodies – Contraindicated in your case

HBV (cont)

Response or no ???Response or no ???High risk practiceTrue non response vs. Waning Ab levelsOne boost to differentiate

– Non response: < 10 IU/l – Responders: > 10 IU/l

NEJM Dec 2004

To boost or not to boost ??To boost or not to boost ??

Currently, there is no proof that booster injections are indicated for the first two decades after successful immunization

After 3rd decade: ???? Studies are needed

J clini Virology 2003

Influenza vaccineInfluenza vaccine

AnnuallyIn the fall season

– even if late 2 strains of A + 1 strain of BNo protection against other Flu like illnesses

like– RSV– Para influenza– Adenovirus

Influenza vaccineInfluenza vaccine

Weak or no association with Guillain Barre syndrome– 1 / million

Contraindication– Previous GB syndrome– ? Egg allergy– Allergic reaction to any component

Prevention - RubellaPrevention - Rubella Rubella IgG +

Immune_

Non-Immune

MMR (avoid pregnancy x 2 m)

Check titers_

Booster_

Inform patient+

Immune

2 months

Rubella-riskRubella-riskRisk of congenital infection

1 + 2 month: 90% 3rd month 50%

Termination of pregnancy is usually recommended in Western countries

> 16 weeks negligible 12 – 16 weeks: deafness can occur

• Congenital rubella syndrome: • growth retardation; malformations of the heart, eyes, or brain; deafness; and liver, spleen, and bone marrow problems.

Prevention - VaricellaPrevention - Varicella

Varicella– History of chicken pox: … immune– Positive titers ….. . .. . . immune

– Absent titers: not immune Give vaccine: 2 doses, 2 months apart

– Postpone pregnancy 2 m after the second dose

Tetanus - Diphtheria vaccineTetanus - Diphtheria vaccine

Once every ten yearsToxoid vaccine

Peneumococcal vaccinePeneumococcal vaccine

Indicated for all immunocompromised adults

> 65 years1 or 2 doses

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