The Bugs The Bugs The Drugs



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The Bugs

  • The Bugs

  • The Drugs

  • ‘La Resistance’

  • Clinical Scenarios from the Children’s Hospital



Earliest bacterial fossil is 3.5 billion years old

  • Earliest bacterial fossil is 3.5 billion years old

    • Cyanobacteria from Archean rock (W. Australia)
    • Small, unicellular
    • Aquatic & photosynthetic (chloroplast in plants)








10 times as many bacteria as human cells in the body (~1014 versus 1013)

  • 10 times as many bacteria as human cells in the body (~1014 versus 1013)

  • 500 to 1000 species of bacteria live in the human gut and a similar number on the skin

  • On the whole, symbiotic relationship between bacteria and host





Simple, efficient and highly adaptable

  • Simple, efficient and highly adaptable

    • Free floating DNA (nucloid) with plasmids














β-lactams

  • β-lactams

  • Penicillin, Amoxicillin O/IV

  • Flucloxacillin (O)/IV

  • Piperacillin/tazobactam IV

  • Amoxicillin/clavulanate O/IV

  • Meropenem IV



Aminoglycosides IV

  • Aminoglycosides IV

    • Gentamycin
    • Tobramycin
    • Amikacin
  • Glycopeptides IV

    • Vancomycin
    • Teicoplanin


Bacteriostatic Antibiotics

  • Bacteriostatic Antibiotics

    • Inhibit bacterial cell growth
    • Need intact immune system to fight infection
    • Clindamycin, Linezolid, Macrolides
  • Bacteriocidal Antibiotics



Clindamycin

  • Clindamycin

    • Binds to 50s ribosomal subunit of the bacteria
    • Inhibits protein synthesis
      • Changes in the cell wall surface which decreases adherence of bacteria to host cells and increases intracellular killing of organisms
    • Reduction in toxin production in
      • Staphylococcus aureus and Group A Streptococcus TSS
    • Exerts an extended postantibiotic effect against some strains of bacteria (attributed to persistence of the drug at the ribosomal binding site)




High (>90%)

  • High (>90%)

    • Cefalexin
    • Clindamycin
    • Rifampicin
    • Fusidic acid
    • Levofloxacin (99%)
    • Metronidazole
    • Linezolid (100%)


Do not use flucloxacillin (clindamycin) suspensions!!

  • Do not use flucloxacillin (clindamycin) suspensions!!

  • flucloxacillin  cefalexin



Penetration of various drugs in CSF

  • Penetration of various drugs in CSF

    • Increases with inflammation, lipid solubility
    • Decreases with molecular weight, protein binding


Good

    • Good
    • Cefotaxime
    • Ceftriaxone
    • Meropenem
    • Metronidazole
    • Ciprofloxacin
    • Vancomycin*


Flucloxacillin/Cefalexin

  • Flucloxacillin/Cefalexin

  • Clindamycin/Fluoroquinolones

  • + Rifampicin/Fusidic acid

  • [3rd generation cephalosporins]



Ampicillin + Gentamicin for Enterococcus spp.

  • Ampicillin + Gentamicin for Enterococcus spp.

  • Flucloxacillin + Gentamcin for MSSA endocarditis

  • Double Gram -ve for Pseudomonas spp. ??

  • Add Clindamycin in SA/GAS TSS

  • Add Rifampicin when foreign material present



Spectrum of activity/Sensitivities

  • Spectrum of activity/Sensitivities

  • Oral/IV forms

  • Static/Cidal

  • PK/PD parameters

  • Bioavailability/palatability

  • Achievable plasma levels/tissue penetration

  • Renal/Hepatic dysfunction







Decreased Permeability

  • Decreased Permeability

    • Porin mutations, efflux system
  • Enzymatic Drug Modification

    • Β-Lactamase (ESBL), carbapenemase production
  • Altered Drug Target

    • PBP2’MRSA, DNA Gyrase mutation
  • Metabolic Bypass

    • Sulfonamides
  • Tolerance

    • Inhibition/killing discrepancy












8yo boy in A&E with 5cm boil on buttocks

  • 8yo boy in A&E with 5cm boil on buttocks

  • On Flucloxacillin for 3 days – not improving

  • History of recurrent boils / cellulitis in last year

  • Obs stable, clinically well





I&D

  • I&D

  • Co-amoxiclav

  • I&D + co-amoxiclav

  • Septrin

  • I&D + Septrin



I&D

  • I&D

  • Co-amoxiclav

  • I&D + co-amoxiclav

  • Septrin

  • I&D + Septrin



Swap and swab!

  • Swap and swab!

  • I&D is key (sometimes enough)

  • What abx are effective for MRSA?

    • TMP/SMX, Erythomycin, Clindamycin (variable, D-test)
    • Rifampicin, Fusidic acid (never alone)
    • Vancomycin, Teicoplanin
    • Daptomycin, Linezolid
  • What is not effective: ANY β-lactam (PBP2’ mutation)



8 years male, short bowel, TPN dependent

  • 8 years male, short bowel, TPN dependent

  • Previous central line (Broviac) infections

  • Frequent hospitalisation

  • Febrile 39.5c in A&E, Hypotensive

  • Needing fluid bolus



Ceftriaxone

  • Ceftriaxone

  • Vancomycin + Ceftriaxone

  • Piperacillin/Tazobactam

  • Ciprofloxacin

  • Vancomycin + Ciprofloxacin

  • Meropenem



Ceftriaxone

  • Ceftriaxone

  • Vancomycin + Ceftriaxone

  • Piperacillin/Tazobactam

  • Ciprofloxacin

  • Vancomycin + Ciprofloxacin

  • Meropenem





At risk for hospital acquired MDR infections:

  • At risk for hospital acquired MDR infections:

    • ESBL – plasmid mediated
      • Klebsiella, E.coli, Enterobacter spp.
    • AmpC – chromosomally induced
      • Serretia, Acinetobacter, Citrobacter, Enterobacter spp.
    • CRE – carbapenem resistant Enterobacteriaceae
  • No Cephalosporins

  • Ciprofloxacin/mero (+/- Glycopeptide/AG if CVL) if septic



3 yo old female

  • 3 yo old female

  • Unwell for 3 days with coryza/headaches (January)

  • Now in A&E, T 40c, Fluid bolusesx3

  • Respiratory Distress Rapid sequence intubation

  • Diffuse erythrodermic rash, rapidly spreading





Oseltamivir + Cefuroxime

  • Oseltamivir + Cefuroxime

  • Cefuroxime + Clarythromycin

  • Cefuroxime + Clindamycin

  • Oseltamivir + Cefuroxime + Clindamycin

  • Oseltamivir + Vancomycin + Meropenem



Oseltamivir + Cefuroxime

  • Oseltamivir + Cefuroxime

  • Cefuroxime + Clarythromycin

  • Cefuroxime + Clindamycin

  • Oseltamivir + Cefuroxime + Clindamycin

  • Oseltamivir + Vancomycin + Meropenem



Viral-Bacterial co-infections, especially with flu

  • Viral-Bacterial co-infections, especially with flu

    • H1N1+GAS, H1N1+SA
  • Add Clindamycin to Penicillin/Cephalosporin

    • Inhibition production of TSST-1 by 95%*
  • Cefuroxime dose – always 50mg/kg!

  • IVIG



2 yo with history of earache and fever

  • 2 yo with history of earache and fever

  • Secondary development of mastoiditis

  • Transfer to Alder Hey for further management

  • Bloods Wbc 17.5, N11.6, CRP 150

  • CT scan and Drainage in theatre





Cefotaxime + Amoxicillin

  • Cefotaxime + Amoxicillin

  • Amoxicillin + Metronidazole

  • Cefotaxime + Metronidazole

  • Vancomycin + Cefotaxime + Metronidazole

  • Vancomycin + Meropenem



Cefotaxime + Amoxicillin

  • Cefotaxime + Amoxicillin

  • Amoxicillin + Metronidazole

  • Cefotaxime + Metronidazole

  • Vancomycin + Cefotaxime + Metronidazole

  • Vancomycin + Meropenem



Microbiology from drainage negative

  • Microbiology from drainage negative

  • Patient improving clinically

    • No fever within 48-72 hours
    • CRP down to 58 then 6 after 1 week therapy
  • Surgeons want to send patient home

  • Still no agreement whether intracranial collection real…



Switch to oral co-amoxiclav x 4 wks

  • Switch to oral co-amoxiclav x 4 wks

  • Switch to oral cefalexin and metronidazole x 6 wks

  • Switch to oral septrin and metronidazole x 6 wks

  • Continue IV ceftriaxone + metronidazole x 6 wks



Switch to oral co-amoxiclav x 4 wks

  • Switch to oral co-amoxiclav x 4 wks

  • Switch to oral cefalexin and metronidazole x 6 wks

  • Switch to oral septrin and metronidazole x 6 wks

  • Continue IV ceftriaxone + metronidazole x 6 wks



No Consensus on IV to oral switch

  • No Consensus on IV to oral switch

  • IV 6 weeks with cefotaxime + metro standard

  • Switch at 2-3 weeks to oral agent only if uncomplicated and good response

    • Oral agent with good CSF penetration
  • Need for multicenter study



3 month old female

  • 3 month old female

  • Gastroschisis repair at birth

  • TPN dependent, Central line in situ

  • Colonised with CRE

  • Fever 38.9c, unwell, vomiting

  • Started on Teicoplanin + Gentamicin IV



Staphylococcus epidermidis in Blood culture

  • Staphylococcus epidermidis in Blood culture

  • Teico MIC=2µ=mg/L, vanco MIC=2mg/L

  • Both Sensitive

    • Breakpoint is 2 for vancomycin, 4 for Teicoplanin
  • No access to Teicoplanin levels



Continue with Teicoplanin high dose -10 mg/kg od

  • Continue with Teicoplanin high dose -10 mg/kg od

  • Add Rifampicin to Teicoplanin

  • Change to Vancomycin and aim levels 15-20mg/L

  • Change to Linezolid

  • Change to Daptomycin



Continue with Teicoplanin high dose -10 mg/kg od

  • Continue with Teicoplanin high dose -10 mg/kg od

  • Add Rifampicin to HD Teicoplanin

  • Change to Vancomycin and aim levels 15-20mg/L

  • Change to Linezolid

  • Change to Daptomycin



Switched to vancomycin 15 mg/kg q8hrs

  • Switched to vancomycin 15 mg/kg q8hrs

  • Blood culture taken when switched is still +ve for same organism

  • Through level of Vancomycin

    • Before third dose – 5.6mg/L, dose 30 mg/kg
    • 24 hours later – 6.0mg/L, dose increased to 35mg/kg
    • 24 later – 8.9mg/L
  • Repeat Blood culture 4 days from initial +ve culture still positive…



Add oral rifampicin

  • Add oral rifampicin

  • Increase dose of vancomycin to 40 mg/kg

  • Switch to linezolid

  • Switch to daptomycin

  • Take line out



Add oral rifampicin

  • Add oral rifampicin

  • Increase dose of vancomycin by 25%

  • Switch to linezolid

  • Switch to daptomycin

  • Take line out



Started on linezolid IV

  • Started on linezolid IV

    • ?Role for loading dose of Vancomycin (30mg/kg)
  • Repeat blood culture negative

  • 1 week later, unwell fever, bolus of fluid

  • Growth of yeast within 24 hours



Start Liposomal amphotericin 3mg/kg od

  • Start Liposomal amphotericin 3mg/kg od

  • Start Fluconazole 12mg/kg od

  • Start Caspofungin 50mg/m2 od

  • Start Micafungin 2mg/kg od

  • ±Take line out



Start Liposomal amphotericin 3mg/kg od

  • Start Liposomal amphotericin 3mg/kg od

  • Start Fluconazole 12mg/kg od

  • Start Caspofungin 50mg/m2 od

  • Start Micafungin 2mg/kg od

  • ±Take line out



Yeast Identified as Candida albicans

  • Yeast Identified as Candida albicans

  • Succesfully treated with

    • 2 week course linezolid
    • 2 week course micafungin  fluconazole
  • Still in Hospital, isolated



Know your friends and your enemies

  • Know your friends and your enemies

    • Basic microbiological knowledge paramount
  • Drug classes and spectrum of activity

    • Quirks: bioavailability, taste, tissue penetration…
  • Be Aware of resistance

    • Hitting hard first then narrow spectrum…
  • Every clinical case is unique

    • Understand each antimicrobials individual strengths
    • Individualised therapy in severe infection


www.bugsanddrugs.ca (www.dobugsneeddrugs.ca)

  • www.bugsanddrugs.ca (www.dobugsneeddrugs.ca)

  • Sandford antimicrobial guide

  • Mandell, Sarah Long textbook

  • Your microbiology lab

  • Promed

  • HPA





Kataloq: wp-content -> uploads -> 2017

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