The Bugs The Bugs The Drugs

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

• Kill bacteria directly
• Do not rely on immune system of patient
• β-lactams, Aminoglycosides, Quinolones, Vancomycin

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