A Romp Through Antimicrobials
A Romp Through Antimicrobials
A Romp Through Antimicrobials
N H OConnell
Bacteriology
Cocci
Peptostreptococci ()
Staphylococci
Coagulase test
+
S aureus Coag neg
Staph
Streptococci
Haemolytic
Alpha
Non-haemolytic
Cocci
Neisseria
Moraxella
Veillonae ()
Bacilli ----- Coliforms
E coli,Klebsiella,Salm /
Shigella
Enterobacteur,
Citrobacteur, Serratia,
Morganella
Non-fermenters
Pseudomonas
Stenotrophomonas
Haemophilus
Pasteurella
Bacteroides ()
Choosing an antibiotic
Spectrum of activity
Bacterio static or cidal
Tissue concentration
Route of administration
Side-effects
Drug interactions
Development of resistance
Cost
Indication
Prophylactic
Empiric
Tailored
Sensitivity Testing
MIC- Minimum Inhibitory Concentration
Sensitive- predictive of favorable outcome
Resistant predictive of poor outcome
Antimicrobial Resistance
Target modification
Drug destruction
Drug modification
Active drug removal
Impermeability
Intrinsic
Acquired
Plasmids
Mobile genetic elements
Mutational
Background
Major Nosocomial Pathogens of the
20th Century and Beyond Four Eras
Gram negatives
Penicillins
1950
Tetracyclines
Aminoglycosides
Macrolides
Polymyxins
Cephalosporins
1990
Carbapenems
1970
1980
Quinolones
Glycopeptides
Linezolid
Streptogramins
Daptomycin
Dalbavancin
Retapamulin
Tigecycline
1960
2000
????
Mode of action
Beta- lactams
Penicillins
Penicillin 1929-40
Flucloxacillin / Methicillin
Ampicillin / Amoxicillin
Co- amoxiclav
Pipercillin / Tazobactam
Cephalosporins
Carbapenems
Imipenem 87-89
Ertapenem 2003
Monobactams
Aztreonam
Mode of action
Act on cell wall, disrupting integrity.
Bactericidal
Generally safe, except for patients with
hypersensitivity
Penicillins
Narrow : Pen G, Pen V
Narrow with anti-Staph:
Fluclox
Mod spectrum : aminoAmpicillin
Broad spectrum:
Beta- lactamase
inhibitors- Augmetin
Broad spectrum with
antipseudomonal:
ureidopenicillinsTazocin
Cephalosporins
First generation:
Cephradine / Cephalothin
Second generation:
Increased activity against
Staph + haemophilusCefuroxime
Third generation:
cefotaxime / ceftriaxone /
cefazidime
Fourth generation:
Cefpirome
Carbapenems
Imipenem +
meropenem
Excellent activity
against enteric Gramnegatives,
Pseudomonas +
anaerobes
No activity against
MRSA, atypical
organisms, E faecium,
Stenotrophomonas
Monobactams
Aztreonam
Useful in penicillin
allergy
Gram-negative
activity only but not
against anaerobes!
Glycopeptides
Active against wide range of Gram positive
organisms
MRSA or methicillin resistant Coag neg Staph
(Staph. epidermidis)
Penicillin- allergic patients: e.g with Strep
pneumoniae
CDAD
Vancomycin
Teicoplanin
Macrolides
Azithromycin, clarithromycin, erythromycin have
wide spectrum of activity
Gram pos cocci, Legionella, Mycoplasma,
Coryne, Chlamydia but not enteric Gram neg
rods
Comm-acq LRTI are indications
Differing half-lives, side-effect profiles,
adsorption
Achieve high intracellular levels
Lincosamides
Active against Gram pos aerobes and
most anaerobes
Significant side effects CDAD
Induce arrhythmias if administered too
quickly
Clindamycin
Tetracyclines
Quinolones
Like cephalosporins, these have
undergone development since 1970s
Nalidixic acid
Ofloxacin and cipropfloxacin
Newer fluoroquinolones: levofloxacin +
moxifloxacin
MIC
S. aureus
S.
pneumoniae
Pseudomon
as
Chlamydia
M TB
Cipro
0.25
1-4
0.25-2 0.5-2
Levo
0.25
0.25-1 0.25
Moxi
0.125
0.5
0.25-1 0.25
0.25-4
Aminoglycosides
30S ribosomal site
Concentration-dependent bactericidal
activity against broad spectrum of aerobic
& facultative Gram-negative bacilli
Toxic patient factors, concomitant drugs,
vol depletion, hepatitic dysfunction, recent
aminoglycosides
Gentamicin, Netilmicin, Amikacin
Oxazolidinones
Sulphonamides
Co-trimoxazole
PCP, Listeria meningitis, Nocardia
Hypersensitivty
Past found widespread use as a broadspectrum agent
Polymixins
Old, discovered in 1947
Nephrotoxic
Polypeptide detergents: interact with
phospholipids in cell membrane
Bactericidal
Braod activity except for Proteus,
Burkholderia, Serratia
Metronidazole
Nitroimidazole
Produces free radicals
Bactericidal
Anaerobic / parasites
Rare development of resistance
Recent
agents
Glycylcycline
Tigecycline
Lipopeptide
Daptomycin
Daptomycin
Rapidly bactericidal3
Average t 89 hours5
Reduction
Result
(hrs)
of the Mean
TAT
(hrs)
All
Organisms
Gram
Positive
Gram
Negative
Mean
Min- Max
Mean
Min- Max
(hrs)
28.62
18.0-60.0
11.12
2.0 27
17.5
27.88
20.0 - 55.0
13.41
2.0 27.0
14.47
28.55
18.0 - 60.0
5.36
2.0 -20.0
23.19
Gram negatives
Penicillins
1950
Tetracyclines
Aminoglycosides
Macrolides
Glycopeptides
Ceftaroline
Polymyxins
Cephalosporins
Quinolones
Aztreonam
1970
1980
1990
2000
Linezolid
Daptomycin
1960
Carbapenems
Tigecycline
2010
CRE/CPE
Carbapenem resistant/ carbapenemase producing
Enterobacteriaceae
Multi-drug resistant Gram-negative organisms
Extremely limited antimicrobial treatment options
First reported case in Ireland in 2009-MWRHL
First Outbreak Ireland 2011-MWRHL
Four hospitals reported CRE outbreaks in 2011-2 UHL
CRE infection is notifiable to public health
Clostridium difficile
Gram + anaerobic bacterium widely distributed in
both soil and intestinal tracts of animals.
Has >150 PCR ribotypes & 24 toxinotypes
First described 1930s by Hall and OToole
So called difficult because difficult to grow in
conventional media
Part of faecal flora in 50-80% healthy neonates
and 3% of healthy adults.
Stool carriage reaches 16-35% in hospital
inpatients.
HPSC C.
difficile
SubCommittee
May 2013
Sent to
Laboratory
for Analysis
Monitored every 10
minutes for 5 days
Negative
Positive
Identification of microorganism
Culture onto
agar plates
and incubate
for 24 hours
Gram
negative
bacilli
Culture onto
agar plates
and incubate
for 6-8 hours
Biochemical Tests
24 hours
18 hours
Series of
lyses/wash
steps
Formic acid/
Ethanol
Extraction
6-8 hours GNB
2-3 Hours
2 minutes
24 hours GPC
Each
microorganism
has a unique
mass
spectrumcomparison
with Bruker
database
EL
70 year old man
Diabetic
Admitted for investigation of anaemia
Developed cellulitis iv cannula site
Temp 38, wcc elevated 15.2 (neut)
BC taken, commenced on IV antibiotics.
EL
? Likely Pathogens
EL
? Likely Pathogens
Staphylococcus
Streptococcus
Which antibiotics?
EL
BC taken, commenced on IV
benzylpenicillin and flucloxacillin
Pt stable, afebrile.
?What do you do
Advised vancomycin/teicoplanin if
deteriorated
Skin infections.
Cellulitis.
Erysipilis.
Impedigo.
Pyoderma.
Postpartum sepsis.
Necrotising Fasciitis
MOC
84 yr old lady
Presented with acute confusion, pyrexia 38
and elevated wcc
BC and MSU sent from A&E
MSU >10,000 cmm pus,0 rcc, +++ bacteria
?Antibiotics
MOC
Commenced on
piperacillin/tazobactam by admitting
team
Uncomplicated recovery
MK
MK
? Likely Pathogens-CAP?
EL
? Likely Pathogens
Streptococcus pneumoniae
H influenza
Moraxella catarrhalis
Atypical Pathogens
Legionella species
Mycoplasma species
C pneumoniae
EL
Other
Viral
Klebsiella pneumoniae
Influenza
- chronic alcoholism
Staphylococcus aureus
Adenovirus
Metapneumovirus
Pseudomonas aeruginosa
-cystic fibrosis or bronchiectasis
MK
? Significance
?What do
Likely
No
No
contamination ;
central lines
prosthetic material;
prosthetic valves/artificial
joints/shunts
LP
65 YR WOMAN
Hx ESRF-Dialysis-dependant
Recurrent UTI
Admitted from dialysis ward with fever rigors.
Temp 39.5,hypotensive 80/50,HR 120/MIN
Blood cultures ,MSU taken
No urinary symptoms
Chest/abdominal examination normal
CXR normal
?DDX
2.Evaluate complications
What complications SA bacteraemia?
Staphylococci
Staphyloccus aureus.
Bacteraemia-complications infection in
Bone.
Joints.
Abscess-brain/lungs/intraabdominal
Capsule of kidney
Heart Valves-IE
Echocardiogram-Trans-oesophageal;
Infective Endocarditis-mobile lesion MV
Bone scan ; no evidence of osteomyelitis
Completed 4/52 antibiotics
Vancomycin/Rifampicin
OT
53 yr male
Hx cholangiocarcinoma/ERCP biliary stent
placement for obstructive jaundice
Admitted with abdominal pain/fever/temp
38/jaundice
Dx cholangitis
BC taken on admission
Commenced on cefuroxime/metronidazole
Blood cultures positive 18 hrs incubation
Microscopy
Gram negative bacilli
Gram pos cocci in chains ?
Streptococcus
Isolate id;
1.E coli;
resistant to ampicillin,.coamoxyclav,ciprofloxacin,cefuroxime
sensitive to gentamicin/piperacillin-tazobactam
2. Enterococcus Sensitive to ampicillin
Changed to piperacillin-tazobactam
Treatment-10/7 antibiotics, ERCP; change of
blocked stent.
CNS
Specimen Review
F No:C426069
DOB: 08/03/1980
Loc: RGH-AE Doctor: <P>
Date Rec'd:13/05/2014 01:31
C.Ant:~~~~~~ Study:
Clin.Details:~~~~
Spec:CSF
Isolate:*I*
Specimen Number : MB910250W 13/05/2014 u/k CSF
Leucocytes
3330 /ul
Sample 1 RBC:
82580 /ul
Sample 2 RBC:
80175 /ul
Sample 3 RBC:
72900 /ul
Sample sent to Biochemistry,MWRH