Advanced Microbiology Flashcards
(236 cards)
1
Q
What is a fever?
A
• Sign of inflamm & can be a symptom/ sign of infec
• Temp over 38 degrees
• Symptoms;
o Fever ‘burning up’
o Chills, sweats, night sweats (patient’s don’t always tell you about this)
o Rigors (uncontrollable shaking- can’t hold tea with spilling, symmetrical on body, usually associated with feeling cold followed by feeling hot)- usually caused by infec
2
Q
What tests can you use when you suspect an infection?
A
• FBC
o Hb; not much help in infec- but anaemia of chronic disease (normocytic, normochromic) can be caused by infec
o White blood cell count (WCC)- caution- just because it’s normal doesn’t mean patient doesn’t have the diagnosis
- Can be raised in infec but other conditions too (poor specificity)- severe sepsis can lower WCC
- Neutrophils- raised in bacterial infec
- Lymphocytes- raised in viral infec
• Blood C-reactive protein
o Inflamm markers;
- C- rective protein <5mg/L= diagnosis of bacterial much less likely (–ve predicted value may help differentitae between a viral or bacterial infec)
- Procalcitonin <0.5µg/L
- (TRAIL, IL-6, IP-10)
- Raised inflamm markers support diagnosis, -ve markers make infec less likely
• Blood prolactionin (in above bullet point)
• Radiological test; chest x-ray (ring around consolidation);
o Clinical infecs- respiratory
o NB x-rays, computed tomography (CT) scanning & CT combined with PET used to support a diagnosis of infec
- How severe is infec?
o Blood lactate & blood gases can help to i.d. severe sepsis & resp failure
o CURB-65- see how severely ill patient is to see if they need to be hospitalised - What is the pathogen?
o Clues from history
o Most common bacterial cause- Streptococcus pneumoniae
o Penicillin resistance more common in Spain
o Legionella pneumonia can be acquired during hotel stays
- Only 2 reasons to carry out a diagnostic test; improve outcome, provide epidemiologicl data
- Lab plays partial role in microbiological diagnosis- results of history, examination, non-microbiological tests & lab tests combined to male diagnostic hypothesis
If CRP & procalcitonin normal- likely that it’s not bacterial pneumonia so won’t need antibiotics.
3
Q
What are Methods of Microbiological Diagnosis?
A
• Use infec tests to confirm a clinical diagnosis
• Microbiological diagnosis relies on 3 modalities;
o Direct detection
o Culture
o Indirect- Immunological tests (antibody detection)
• Culture tests should be taken before antibiotics given
4
Q
What is the use of culture?
A
• Isolation of viable pathogen enables;
o Identification- immediate or by further testing
o Typing- to establish organism relatedness
o Sensitvity testing- to direct antimicrobial therapy
• Not applicable to non-cultivable micro-organisms
• Needs to be done before antibiotics are started
• Certain organisms die quickly- need to do tests before start giving antibiotics
• Blood culture sampling;
o Coagulase –ve staphylococci normally on skin (can cause infec)- needs to be aspectic technique to avoid contamination
o Can improve sensitivity & specificity by way the blood sample taken
o Put some of culture on plate
o 9. Identification process
o 10. Lab will provide report
5
Q
What is a Gram Stain? What colour are +ve/-ve?
A
• Chemical process that distinguishes cell walls that retain crystal violet & those that don’t when stained & washed with acetone
• This helps to decide which antibiotics they will respond to
• Gram +ve- purple
• Gram –ve- pink (or colour of counter- stain)
• Microbiology will give you gram satin of bacteria & shape of bacteria
• Gram +ve cocci;
o Form chains
o Form clusters
6
Q
What is Sensitivity Testing?
A
• Needs viable micro-organisms- usually bacteria or fungi
• Agar plate spread with a suspension (organism) your interested in
• Put samples of antibiotics
• As organism grows can see which antibiotics it can’t grow around (effective) & which it can (antibiotics it’s resistant to) by measuring zone of inhibition
• Basic principle;
o Culture of micro-organism in presence of anti-microbial agent
o Work out if conc of antimicrobial that will be available in the body is high enough to kill the micro-organism
o Solid or liquid media
7
Q
What are the Uses &limitations of Sensitivity Testing?
A
Uses & limitations
• To inform decisions on targeted antimicrobial therapy;
o Initial treatment with ‘empirical’ therapy
o Subsequent treatment ‘targeted’- need;
Isolation of micro-organism
Antimicrobial susceptibility testing
• The correlation between antimicrobial sensitivity & clinical response is not absolute
• Establishes micro-organism presence at a particular site- cultivable micro-organisms only
• Allows the use of empirical & targeted antimicrobial therapy
• Provides epidemiology & typing info
To inform antibiotic therapy;
• 1st line antibiotic choice if infec doesn’t need immediate treatment e.g. infectious endocarditis, osteomyelitis (unless patient is septic)
• 2nd line choice after empiric therapy (use very broad spectrum, then give specific)- ‘smart smart then focus’
• 2nd line choice after failure of initial therapy- uncomplicated UTI in general practice
To provide epidemiological data- ‘surveillance’;
• Sensitivity results collated locally, nationally & internationally;
o To inform local guidelines &antibiotic choices
o To provide epidemiological data (can work out trends & future resistance)
o To provide early warning of threats to public health
8
Q
What is Direct Detection?
A
• Detection of whole organism- microscopy e.g. CSF from lumbar puncture
• Detection of component of organism; antigen, nucleic acid (DNA or RNA)
• Detection of antigen
o E.g. Legionella antigen detection test
o Adv of doing this at bedside- quick result
o Disadv- needs training, quality control, need to ensure no false +ves
o Target Ags include; polysaccharide capsule (Cr. neoformans), cell wall polysaccharides (Aspergillus galactomannan, Candida mannan).
o Solubility & distrib of Ag differs with infecting species, & is poorly understood for Aspergillus & Candida.
o Serological tests include latex agglutination (Cr. neoformans) & ELISA (Aspergillus galactomannan and Candida mannan).
o Sampling protocol i.e. use of test for screening (low pre-test probability pop’n) vs. diagnostic (high pre-test probability).
o Does result offer any adv over other methods? Does making the diagnosis influence clinical outcome?
• Detection of nucleic acid (DNA/RNA)
o Viruses- influenza
o Bacteria- streptococcus pneumoniae, 16S PCR (all bacteria have ribosomes, primers bind to conservative areas, can compare organisms- can do PCR & i.d. any bacterial pathogen, broad range PCR identifies pathogen)
o Fungi- Candida spp., Aspergillus spp.
9
Q
What are the Uses &limitations of Direct Detection?
A
• Establishes presence of micr-organism at a particular site- cultivable & non-cultivable organisms
• Allows the use of appropriate empiric antimicrobial therapy
• Does NOT give any info on:
o Antimicrobial susceptibility
o Typing
• Is usually the fastest diagnostic method
10
Q
What are Immunological Tests?
A
• Detection of immune response to infec
• Antibody detection
o IgM detection
o Seroconversion- change from –ve to +ve result from 1 test to a subsequent test
o Fourfold rise titre- rise in antibody conc from 1 test to subsequent test
‘Titre’ is 1/greatest dilution at which antibody is detectable
i.e. if antibody is just detectable at a serum dilution of 1/64 the titre is 64
‘Fourfold rise in titre’ would be e.g. 2= 32 or 4=64
• Serological test to look for antibodies; dilute to make serum less & less concentrated in wells in plastic trays, need to do it in pairs (acute & convalescent sample in patient)- if serum converts & no antibodies in acute but lots in convalescent- shows been exposed to pathogen
• E.g. diagnosis of disease in question can be made in Patients B &a; C- showed seroconversion & fourfold rise in titre respectively, Patient A had no signif change in titre between tests, and antibody was not detected at all in patient D
• Other immunological tests
11
Q
What are the Uses & limitations of Antibody Testing?
A
- Confirms exposure to a specific micro-organism- cultivable & non-cultivable organisms
- Is restricted to patients with a detectable antibody response
- Is retrospective- aften too late to inform antimicrobial therapy decisions
12
Q
How do you Choose the Right Antimicrobial Agent?
A
Know the likely organism(s)
• Body site- can be whole body or just e.g. urinary tract UTI
• Immunological status- e.g. depending on how immunosuppressed patient is
• Microbiological history- e.g. skin & soft tissue infec e.g. check they don’t have MRSA as may need to use diff antibiotics
• Microbiological history- if antibiotic they once used failed don’t use again
• Risk factors
1. Select agent with appropriate antimicrobial spectrum- to cover organisms likely causing infec
2. Match the pharmacokinetics to the patient
• Distribution e.g. which antibiotic would go to urine if UTI or CSF if meningeal infec
• Interactions
• Adverse effects
- Empirical & targeted therapy
- Route, duration (review)
- Distrib/ penetration (antibiotics get into site of infec e.g. into CSF for meningitis)
- Bacteriocidal (antibiotics kill microorganism)/ static (antibiotics stop microoganisms growing)
- Resistance
- Special situations e.g. liver/ renal impairement, obesity (some antibiotics need to be given on true/ ideal body weight), young/ elderly, HCAIs (healthcare associated infecs e.g. c. diff)
- Monitoring (e.g. gentamycin or vancomycin)- adequate dose/ levels that cause toxicity)
- Prophylaxis- surgical (e.g. high risk infec surgery) or long-term (suppression)
13
Q
What do Bacteria & Fungi have in Common?
A
- Cell wall (physical protec)
- Cell memb(s) (bacteria may have 2 membs)
- DNA (for protein synthesis)
- Synthetic functions- protein synthesis
- Can use these to target antimicrobial agents
- Synthesis happens in the middle
14
Q
What are the Differences between Bacteria & Fungi ?
A
DNA localisation
• Bacteria are ‘prokaryotes’- their DNA exists as a ring like struc in cytoplasm
• Fungi are ‘eukaryotes’- their DNA separated from cytoplasm by a nuclear memb (nucleus seps DNA & cytoplasm)
Size
• Bacterial cells smaller than fungal cells
Structure
• Bacterial cells uniform simple strucs (e.g. e.coli cells look the same)
• Fungal cells may have complex struc & same organism may have many diff forms (hyphae, spores etc) e.g. spores diff from mushroom
Cellular processes
• Fungal protein & DNA synthesis very similar to human processes (protein & synthesis- harder to use this as a target for antimicrobial treatment
15
Q
What are Antibiotics?
A
• Antibiotics- chem products of microbes that inhibit/ kill other organisms
16
Q
What are Antimicrobial agents ?
A
• Antimicrobial agents (antibacterial, antifungal, antiviral);
o Antibiotics (many made by fungi e.g. penicillin, some made by bacteria)
o Synthetic compounds (not from a microbe) with similar effect to antibiotics e.g. sulphonamide
o Semi-synthetic i.e. modified from antibiotics to make a new compound- diff antimicrobial activity/ spectrum, pharmacological properties or toxicity
• Terms antibiotic & antibacterial agent often used interchangeably
17
Q
What is Bacteriostatic/ fungistatic?
A
• Bacteriostatic/ fungistatic- agent inhibits growth of bacteria/ fungi e.g. protein synthesis inhibitors
18
Q
What are Bacteriocidal/ fungicidal?
A
• Bacteriocidal/ fungicidal- kills organisms e.g. cell wall-active agents
19
Q
What is the Minimum inhibitory concentration (MIC?
A
- Minimum inhibitory concentration (MIC)- minimum antimicrobial conc at which visible growth inhibited in an artificial cuture system, if low MIC- agent active against organism it is being tested (is a good antimicrobial)
- Low MIC (e.g. 0.1 mg/L)= sensitive organism; BUT sensitivity actually depends on level available at site of infec (e.g. might be able to kill organism (have a low MIC) but can’t get into urine)
20
Q
What is the Minimum bactericidal/fungicidal conc ?
A
• Minimum bactericidal/fungicidal conc (MBC/MFC)- minimum conc of antimicrobial agent at which most organisms killed
21
Q
What is the Antimicrobial Spectrum ? When would you use the different types?
A
- Range of bacterial/ fungal species likely to be sensitive to a partic antibacterial/ antifungal agent
- Broad spectrum- kills most types of bacteria/ fungi encountered
- Narrow spectrum- kills only a narrow range of organisms
- Knowledge of antimicrobial spectrum vital in choosing appropriate antimicrobial agent/ combination to treat a given infec
- Aim: use narrowest spectrum agent as possible ideally only kills particular species of bacterium that is causing infec
- E.g. broad spec antibiotic in 6 yrs time might be narrow spec due to antibiotic resistance can now only kill a narrow range
Broad spectrum can decrease enterohepatic cycling= decrease effect of oral contraceptives and fit k synthesis. Can also increase INR and affect warfarin
22
Q
What are features of the Bacterial Cell Wall?
A
• Gives bacteria structural rigidity
• Peptidoglycan;
o In gram –ve & +ve
o Polymer of glucose-derivatives, N-acetyl muramic acid (NAM) & N-acetyl glucosamine (NAG)
• Animal cells don’t have a cell wall- ideal potential for selective toxicity
23
Q
What are features of the Fungal Cell Wall?
A
• Β-1,3-glucan
o Large polymer of UDP-glucose
o 50-60% of dry weight of fungal cell wall
o Synthesized by β-1,3-glucan synthase
• Also has some chitin in it (small proportion &; no anti-fungal agents aimed at chitin)
• Animal cells don’t have a cell wall- ideal potential for selective toxicity
24
Q
What are antibacterial Cell Wall Synthesis Inhibitors?
A
- β-lactams (big class of antibiotics)
- Glycopeptides (smaller antibiotic class)
Other clinically useful cell wall synthesis inhibitors; cycloserine (anti-tuberculous agent) & fosfomycin (antibacterial but not available in UK)
25
What are Anti-fungal Cell Wall Synthesis Inhibitors?
• Echinocandins (antifungal class)
26
What are β-Lactam Antibiotics?
* 1st true antibiotics in clinical practise- Benzylpenicilin (penicillin G);acid labile so give parenterally
* All contain β-lactem ring; 4-membered ring struc (C-C-C-N), forms a structural analogue of D-alanyl-D-alanine
* Interfere with ‘penicillin binding proteins’ (enzymes involved in synthesis & maintenance of peptidoglycan) function; transpeptidase enzymes involved in peptidoglycan cross-linking (if stop these cell dies)
* Most widely prescribed of antibacterial antibiotics
* Phenoxymethyl penicillin (penicillin V) 1st oral penicillin
* Ampicillin 1st penicillin with activity against Enterobacteriaceae fam, can only be delivered parenterally (oral equivalent is amoxicillin)
* Meticillin- anti-staphylococcal penicillin (side chain prevents it being hydrolysed by staphylococcal b-lactamase)
* Has been superceeded by drugs such as cloxacillin & flucloxacilin
27
What are the different β-Lactam Antibiotics Classes?
• Penicillins;
o Benzylpenicillin, amoxicillin, flucloxacillin
o Relatively narrow spectrum
o Ends with ‘cilin’ is a beta lactam so if someone allergic to penicillin they are allergic to all drugs ending in ‘cillin’ (types of penicillins)
• Cephalosporins (all start with ‘cef’);
o Cefuroxime, ceftazidime etc
o Arranged into ‘generations’
• Carbapenems
o Meropenem, imipenem
o Extremely broad spectrum
• Monobactems
o Aztreonam (not bi-cyclic only has 1 ring, gram –ve activity only)- considered safe to give in penicillin allergy
28
What are Penicillins?
β-Lactam Antibiotics
o Benzylpenicillin, amoxicillin, flucloxacillin
o Relatively narrow spectrum
o Ends with ‘cilin’ is a beta lactam so if someone allergic to penicillin they are allergic to all drugs ending in ‘cillin’ (types of penicillins)
29
What are Cephalosporins?
β-Lactam Antibiotics
o Cefuroxime, ceftazidime etc
o Arranged into ‘generations’
30
What are Carbapenems?
β-Lactam Antibiotics
o Meropenem, imipenem
o Extremely broad spectrum
31
What are Monobactems?
```
β-Lactam Antibiotics
o Aztreonam (not bi-cyclic only has 1 ring, gram –ve activity only)- considered safe to give in penicillin allergy
```
32
What are β-lactamase Enzymes?
• Hydrolyse (inactive) β-lactams
• Common mechanism of resistance to β-lactam antibiotics
• Diff β-lactamse enzymes confer resistance to a narrow/ wide range of β-lactams e.g.;
o Staphylococcal β-lactamase- some penicillins only
o ‘Extended spectrum β-lactamsae’ (ESBL)- penicillins & cephalosporins
o Carbapenemases (e.g. NDM1)- cebapenems
33
What are β-lactam/β-lactamase Inhibitor Combinations (BLBLI)?
* Give combination drug- antibiotic drug & another chemical that inhibits beta lactamase (if organism uses this to inhibit antibiotic)
* Amocixillin- clavulanate (Augmentin)- increases spectrum of amoxicillin
* Piperacilin-tazobactam (Tazocin)- increases the spectrum of pipercillin
* Alavulanate & tazobactam stop it breaking down antibiotic
* ESBL & carbapenemase BLBLIs- work in progress
* Probs with BLBLIs;
* Very broad spectrum, so predispose to C.difficile infec
* Names don’t end with –illin or start with cef- (easy to forget these are penicillins)= importance of penicillin allergy may be missed (don’t give to someone who has a penicillin allergy)
34
What are Glycopeptides?
Glycopeptides (Antibacetrial)
• Vancomycin, teicoplanin
• Large molecules, bind directly to terminal D-alanyl-D-alanine on NAM pentapeptides- inhibit binding of transpeptidases & so peptidoglycan cross-linking
• Gram-positive activity- can’t penetrate gram-ve outer memb porins
35
What are Echinocandins?
Echinocandins (antifungal)
Mode of action;
• Inhibit of β-1,3-glucan synthase (makes beta 1,3- glucan)
• Construction of severely abnormal cell wall
Examples;
• Anidulafungin
• Caspofungin
• Micafungin
Protein synthesis in bacteria
• RNA translation= protein takes place on ribosome
• Ribonucleoprotein complexes (2/3 RNA, 1/3 protein)
• 50S (large) and 30S (small) subunits combine to form 70S initiation complex (makes protein)
• S=Svedberg units; relative sedimentation rate
36
What are common classes of Protein Synthesis Inhibitors?
Aminoglycosides
MLS antibiotics
Tetracyclines
Oxazolidinones
37
What are Aminoglycosides ?
Protein Synthesis Inhibitors
• Gentimicin, amikacin
• Bind to 30S ribosomal subunit
• Mechanism of action not fully understood
38
What are MLS antibiotics ?
Protein Synthesis Inhibitors
• Macrolides, Licosamides, Streptogramins
o Erythromycin, clarithromycin (macrolides)
o Clindamycin (lincosamide) (pre-dispose to c.diff so used less); bind to 50S ribosomal subunit, inhibit protein elongation
39
What are Tetracyclines?
Protein Synthesis Inhibitors
• Tertacycline, doxycycline (type of tetracycline)
o Bind to 30S ribosomal subunit
o Inhibit translation by interfering with tRNA binding to rRNA
• Tigecycline- modern derivative of tetracyclines with a similar mechanism of action & broader spectrum
40
What are Oxazolidinones?
Protein Synthesis Inhibitors
• Linezolid
o Inhibits protein synthesis inititation
o Bids to 50S ribosomal subunit
o Inhibits assembly of initiation comples
o May also bind to 70S subunit
o Traets MRSA infec of chest & skin & soft tissue infecs
• Other antibacterial protein synthesis inhibitors
o Mupirocin (bacteroban is trade name)
o Fusidic acid
41
What are Protein Synthesis inhibitors in Fungi?
NONE
• Fungi are eukaryotes- have same protein synthesis mechanisms as humans
• So protein synthesis not a target for antifungal agents
42
What are common classes of DNA Synthesis Inhibitors?
Trimethoprim & sulfonamides
| Quinolones & Fluoroquinolones
43
What are Trimethoprim & sulfonamides?
Trimethoprim &sulfonamides
• Both inhibit folate synthesis
o Trimethoprim- dihydrofolate reductase
o Sulfonamides- dihydropteroate synthetase
o Folic acid is a purine synthesis precursor
o Many bacteria make folic acid from para-aminobenzoic acid- this pathway target for sulphonamides & trimethorprim
o In vitro tests- sulphonamides & trimethoprim synergistic but not when this combo used to treat bacterial infecs
• Trimethoprim
o Commonly used to treat UTI (broad spectrum for gram –ves that cause UTI)
o Oral
• Co-trimoxazole (trimethoprim-sulfamethoxazole)
o Mainly an antibacterial agent but also affective against Pneumocystis jirowecii (funagal cause of pneumonia in HIV patients & other immunosuppressed agents)
44
What are Quinolones & Fluoroquinolones?
• Inhibit 1 or more of 2 related bacterial enzymes
o DNA gyrase & topoisomerase IV
o Involved in DNA remodelling during DNA replication
• E.g. nalidixic acid, ciprofloxacin (used in UTIs), levofloxacin
• Quinolones only effective against bacteria
Quinolones can cause tendonitis and convulsions if given with steroids/NSAIDs
Anything that gives clues that say don’t take with milk- can cuase sticky mess in your stomach
45
What DNA Synthesis Inhibitor is used for Fungi ?
* 5 fluorocytosine (5FC) is a fungal DNA inhibitor, developed as a putative anti-cancer drug
* Selectively taken into fungal cells by a fungal enzyme (cytosine permease- fungus specific enzymes, so gets into fungal cells not human cells)
* Selective toxicity poor
* Not used very much
46
What is Rifampicin?
RNA Synthesis Inhibitor
• Rifampicin- RNA polymerase inhibitor- prevents mRNA synthesis
• Cornerstone of anti-tuberculous chemotherapy
Anything that gives clues that say don’t take with milk, or antacids- can cuase sticky mess in your stomach
47
What are Antibacterial Cell Membrane Agents?
o Colistin (gram –ves)- only effective against gram –ves
o Daptomycin (gram +ves)- only used against gram +ves
Cyclic lipopeptides (have a ring struc)
Destruc of outer memb/ cytoplasmic memb (lipophilic tail inserts in here)
48
What are Anti-fungal Cell Membrane Agents ?
o Azoles (e.g. clotrimazole (vaginal thrush), fluconazole)
o Terbinafine- inhibit ergosterol synthesis (a component of fungal cell membs but not human/ bacterial cells)
o Amphotericin B (& nystatin)- bind to ergosterol causing physical damage to fungal memb
49
What is Antimicrobial Combination Therapy? Why is it used?
Antimicrobial Combination Therapy
Reasons for combining antimicrobial agents;
• To provide adequaltely broad spectrum- single agent might not cover all required organisms;
o Polymicrobial infec (multiple n=bacteria or bacteria + fungi)
o Empiric treatment of sepsis
• To increase efficacy - synergistic combination may improve outcome
o β-lactam/aminoglycoside in streptococcal endocarditis
o Cell wall agent/ protein inhibitor in severe Group A streptococcal infec
• To reduce resistance- organism would need to develop resistance to multiple agents simultaneously
o Antituberculosis chemotherapy
50
What is Amphotericin B?
Inhibits Cell membrane integrity in fungi
51
What is Daptomycin?
Inhibits cytoplasmic membrane in bacteria
52
What is Colistin?
Inhibits outer membrane in bacteria
53
What are the Causes of Antibiotic Resistance?
* Mixture of sensitive & resistant bacterial strains exposed to antibiotics
* Sensitive strains- die out, resistant strains- become dominant colonising strains of that person
* Antibiotic-resistant strains more likely to cause subsequent endogenous infec (infec caused by patient’s colonising flora)
* Antibiotic-resistant strains may be transferred to other people (potential recipients of resistance)
* Large bowel- repository for many organisms
* If treat patient with antibiotics then take sputum sample- will grow gram –ve bacteria resistant to antibiotic (no clinical relevance here- but shows once give antibiotics will effect normal bacteria)
54
What are innate Resistance Mechanisms ?
• Fundamental property of bacterium/ antibiotic condition
• Usually relates to permeability/ entry of antibiotic into cell
o Gram –ves resistant to; glycopeptides, daptomycin (cell wall active agents, large molecules, can’t penetrate gram –ve outer memb- not effective against gram –ve bacteria so innate resistance in all gram –ve bacteria to glycopeptides & daptomycin)
o Gram +ves resistant to; aztreonam (only affective against gram –ves), colistin (works on gram –ve outer memb, gram +ves don’t have outer memb so won’t work on them)
o Anaerobes resistant to; aminoglycosides (e.g. gentamycin) don’t work (as need oxygen dependant transport mechanisms to get aminoglycosides into cells but anaerobes don’t have this mechanism)
o Streptococci resistant to; aminoglycosides but treated with gentimycin & penicillin together (as penicillin allows gentimycin to work)
55
What are acquired Resistance Mechanisms ?
• Organism acquires gene that encodes antibiotic resistance mechanism
o New mutation in organism (gives organism survival adv in presence of an antibiotic)
o Horizontal transfer of genetic material to another source
• Usually an antibiotic-modifying enzyme (destroys antibiotic) or target alteration (causes gene for antibiotic target to be altered in some way)
56
What are types of acquired changes in bacteria?
1. Absent target
• Antibacterial agents/fungi
• Antiviral agents/ bacteria
• If treat fungal with anti-bacterial agent, fungal cell walls made of diff substance so antibiotic won’t work, or e.g. antibiotic won’t work in viral infec
2. Decreased permeability (common cause of innate resistance)
• Vancomycin: Gram –ve bacilli (gram –ves have an outer memb impermeable to vancomycin)
• Gentamicin: anaerobic organisms (aminoglycosides uptake needs O2 dependant active transport mechanism not present in anaerobes)
• Most antibacterial needs to get INSIDE cell e.g. bacterium coverings may not allow antibiotic to get inside
3. Target modification
• Antibiotic can no longer react with agent
• Flucloxacillin: MRSA
o Altered penicillin-binding protein (PBP2- encoded by MecA gene) doesn’t bind β-lactams
• Vancomycin resistant enterococci: VRE
o Acquired a gene which altered peptide sequence in gram +ve peptidoglycan (D-ala D-ala D-ala D-lac)
o Reduces vancomycin binding 100 fold so it doesn’t work
• Trimethoprim: gram –ve bacilli
o Mutations in dhr (dihydrofolate reductase gene)
4. Enzymatic degradation
• Drug acquired gene which codes enzyme (β lactamases)- causes enzyme to be hydrolysed (common resistance mechanism for β lactems) e.g. saph aureus rarely sensitive to penicillin now (has penicillinase)
• Penicilins & cephalosporins: β-lactamases
o Staphylococcal penicillinase (inactive penicillin/ amoxicillin)
o Extended-spectrum β-lactamases (ESBL); act against larger spectrum of β lactems, inactivate penicillins & cephalosporins, common resistance mechanism against gram –ve bacteria
o Carbapenemases (enzyme- degrade carbopenems)
• Gentamicin: aminoglycoside modifying enzymes modify it
• Chloramphenicol: degraded by chloramphenicol acetyltransferase (CAT)
5. Drug efflux
• Multiple antibiotics, specially in gram –ve organisms
• Antifungal triazoles & Candidia spp
• Transfers drug if gets into organism straight back out of organism
57
What are is vertical/horizontal spread of resistance?
• Many resistance mechanisms encoded by single genes e.g. antibiotic modifying enzymes, altered antibiotic targets
• Resistance genes encoded in plasmids; circular DNA sequences transmitted within & between species mainly by conjugation
• Bacterial genome- plasmins replicate around bacterial genome; can transfer gene to bacterial genome (free transfer between genome & plasmid), can cause resistance in cell plasmid is in, can transfer to other cells
• Horizontal transfer;
o Enabled by transposons & integrons
o Integrons- DNA sequences designed to be transferred from plasmid to plasmid and/or from plasmid to chromosome
o Often contain ‘cassettes’ with multiple resistance genes
o Usually intra-species
• Vertical transfer;
o Bacterial cells divide transferring chromosomal or plasmid-borne resistance genes to daughter cells
o Once bacteria has resistance gene- undergoes replication by binary fission so all replicated cells have it (is propagated through the generations)
58
What is pan-resistant gram –ve bacilli?
resistant to everything
59
What are the Practical Consequences of Antibiotic Resistance?
Bacterial infecs become resistant to antibiotics traditionally used to treat them e.g.
• Meticillin-resistant Staphylococcus aureus (MRSA) resistant to flucocycilin ?
• Vancomycin/glycopeptide-resistant enterococci (VRE/GRE)
• Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL)
• Carbapenemase-producing Enterobacteriaceae (CPE)
• Multi-drug resistant tuburculosis (MDR-TB)
• Extremely-drug resistant tuberculosis (XDR-TB)
• Others;
o Enterobacteriaceae resistant to amoxicillin, ciprofloxacin, gentamicin, carbapenems etc.
o Pseudomonas resistant to ceftazidime, carbapenems etc.
60
How do you Monitor Antimicrobial Resistance?
Sensitivity testing;
• Culture micro-organism in presence of antimicrobial agent
• Determine whether minimum inhibitory conc (MIC) ia above a predetermined ‘breakpoint level’
o High enough to kill organism
o Sustained at site of infec for long enough using practicable dosing regimens
• If grows at a level of antibiotic that is available in body- is resistant
• If doesn’t- is sensitive
Dis-sensitivity testing;
1. Add organism
2. Put antibiotic impregnated filter discs- antibiotics diffuse out from disc outwards so highest in middle & lowest in outer edges
3. Incubate
4. Read & interpret results- zone of inhibition (if too small- doesn’t kill microoganism/ need such a vast conc of antibiotics to kill microorganism can’t give in human)
• In pic- microorganism resistant to 3, 1 not enough sensitivity, 2 antibiotics with enough zone on inhibition
Liquid media- microtitre plate susceptibility testing;
• Liquid culture
• Has wells
• Add antibiotics to plate e.g. have 8 diff antibiotics in plate, then do doubling dilutions with pipette so conc of antibiotic is reduced as move to R of plate (when get to e.g. n.o. 12 conc of antibiotic very low)
• Then add organism (add same amount to each well incubate it, get growth in some wells)
• Further to highest conc of antibiotic it grows- more resistant it is
• Green arrows- breakpoint MIC, compare black arrows with this (lowest where see antibiotic growth)
61
What is the Epidemiology of Antibiotic Resistance?
* Resistance rates vary markedly throughout the world e.g. in Europe resistance highest in the South
* Worldwide resistance ‘hotspots’ e.g. carbapenem resistance in Indian subcontinent
* Diff organisations collect, collate and publish comparative resistance data; European Antimicrobial Resistance Surveillance Network (EARS-Net), Surveillance atlas of infectious disease
* Worldwide epidemiological data- informs local antibiotic & infection prevention & control policies e.g. if person recently been to area that has high carbopenem resistance- screened to see if picked up resistance
62
What are Viruses?
• Consist of;
o Nucleic acid (DNA or RNA)
o Protein (coat- structural, enzymes- non-structural)
• They are obligate intracellular pathogens
• Virus genomes e.g. enterovirus genome less complex compared to DNA herpes virus genome
63
What are Acute Viruses?
Influenza
Measles
Mumps
Hep A
64
What are Chronic Viruses?
Chronic (generally DNA viruses)
• Latent (with/ without recurrences, stay with us lifelong- can still be passed on in secretions); herpes simplex, cytomegalovirus
• Persistent; HIV, HTLV, Hep B, Hep C
• (HIV & HTLV- RNA viruses but act as DNA viruses as convert RNA to DNA
65
What are examples of Virus Syndrome Rashes?
```
Non-vesicular rashes (red lumpy rash);
• Measles
• Rubella
• Parvovirus
• Adenovirus
• HHV6
Vesicular rashes (start as macular popular rash then become fluid filled);
• Chickenpox (HHV3)
• Herpes simples (HHV1/2)
• Enterovirus
```
66
What are examples of Virus Syndrome Respiratory Infections?
* Influenza A/B
* Respiratory Syncytial Virus (in young children causing bronchiolitis- in nov-Dec time)
* Parainfluenza virus
* Human Metapneumovirus
* Rhinovirus
* Coronavirus (including SARS)
67
What are examples of Virus Syndrome Gasteroenteritis ?
* Rotavirus
* Norovirus (often food associated & in hospitals)
* Astrovirus
* Sapovirus
* Adenovirus (group F)
68
What are examples of Virus SyndromeNeurological Disease ?
```
Encephalitis/ meningitis;
• HSV (reactivation)
• Enteroviruses e.g. caused by herpes simplex
• Rabies
• Japanese encephalitis virus
• Nipah Virus
```
69
What are examples of Virus Syndrome Blood-Borne Viruses ?
* Hepatitis viruses; HBV, HCV
* Retroviruses; HIV 1,2 & HTLV 1,2
* (Can be spread via blood, mum to child, injecs)
70
When do you use Antivirals
Acute infections in general population;
• Primary HSV and Herpes simplex encephalitis
• Chickenpox in adolescents and adults
• Shingles in eye (reactivation of varicella zoster virus)
• Extremes of life e.g. neonate or Elderly when T-cell response starts to wane (shingles, influenza)
Chronic infections (signif morbidity & mortality);
• HIV, HBV, HCV
Infections in immunocompromised;
• Post transplant
• Individuals receiving immunosupressive therapies
71
What are the steps in Virus Replication?
1. Virus attachment to cell (via receptor)
2. Cell Entry
3. Virus Uncoating
4. Early proteins produced – viral enzymes
5. Replication
6. Then switches to make late transcription/translation – viral structural proteins
7. Virus assembly
8. Virus release and maturation
• Many viruses don’t affect cell, disease can be caused by immune resposne e.g. hep B in liver, liver will continue function- only if have immune response to hep B will see disease
• Not always the case e.g. with chicken pox- is virus causing the disease
* Viruses take over much of host intracellular machinery
* All viruses encode unique proteins many of which are vital for virus replication and infectivity
* These unique proteins are targets for molecular inhibition (anti-viral activity)
72
Which Polymerases can be inhibited in viruses?
Viruses contain polymerases that convert;
• DNA to DNA; eukaryotes, DNA viruses
• DNA to RNA; eukaryotes, DNA viruses
• RNA to RNA; RNA viruses
• RNA to DNA (reverse transcriptase- DNA then can integrate); retroviruses (HIV), hep B virus
73
What is Azidothymidine?
AZT (Azidothymidine)
• Developed in 1965 as anti-cancer drug
• In 1985 found to inhibit HIV replication (1st HIV drug)
• Nucleoside Reverse Transcriptase (NRTI)- affects reverse transcriptase in polymerising HIV
• Inhibits HIV replication (initially for cancer drug but too toxic dose required, can use for HIV as can use lower dose)
74
What are HIV NRTI?
```
Pyrimidine analogues
• Thymidine analogues- Zidovudine
• Cytosine analogues- Lamivudine
Purine analogues (Adenosine and Guanosine)
• Abacavir
• Tenofovir
```
75
How do you treat Hep B?
• Contains reverse transcriptase enzyme (diff struc to HIV but function in similar way)
• Some NRTIs also active vs HBV
o Lamividine
o Tenofovir
• If duel infection then use these drugs in regime (as Lamividine &; tenofovir treat HIV & hep B)
76
What are Herpesvirus Polymerase Inhibitors?
• Aciclovir
o HSV (herpes simplx) and VZV (vaircella zoster)
o Aciclovir can work at low concs
• Ganciclovir
o CMV (cytomegalovirus), HHV6 (as well as HSV and VZV)
o Broad spec activity, need to use at higher levels
77
What is a HCV RNA Polymerase Nucleotide Inhibitor ?
* Hep C treatments
* Used to use interferons- part of our innate immune system (molecules that target viral infecs- triggers enzymic reacs in cell to destroy virus)
* Can use endogenous interferon to treat viruses
* Have now direct acting anti-virals- sofosbuvir; is monophosphate, is safe & effective
* Strain 3 of Hep c not sensitive to sofosbuvir but is to interferon
78
What are
```
• Viruses contain their own to control their own replication- diff from ones in our own cell so drugs that inhibit these shouldn’t be toxic to our own cells
• HIV
o Atazanavir
o Darunavir
o Ritonavir (now used to boost levels of other PIs)
• HCV
o Paritaprevir
o Grazoprevir
```
79
What is Aspartate Protease of HIV?
• Complex molecule of inhibitor- bind to cell to inhibit it’s replication
80
What are Integrase Inhibitors?
• Integrase Inhibitors (unique enzyme to retroviruses)- make molecules to inhibit this enzyme, not very toxic as we don’t have these enzymes in human genome
o Raltegravir
o Dolutegravir
81
What is Enfuviritide?
```
• Entry inhibitor (as virus needs to bind to & enter cell)
o Enfuviritide (T20, given by IM injection as is a polypeptide) –fusion inhibitor (molecule in HIV which causes fusion)
```
82
What is Maraviro?
• Entry inhibitor (as virus needs to bind to & enter cell)
o Maraviroc - Chemokine receptor antagonsit binds to receps so virus can’t (Co-receptor & CCR-5 receps- predominatly used by HV- needs to bind to this recep)
83
What is Highly Active Antiretroviral Therapy ?
Highly Active Antiretroviral Therapy (HAART)
• For HIV treatment need combo of 3 drugs- as if use 1 drug virus quickly replicates & gets ressitant to it but if use 3 drugs HIV can’t become resistntn to all 3 on time
• Attack at least 2 sites of viral replication e.g. 2 drugs attacks 1 part & ; 3rd drug attacks another part
• HAART;
o 2 NRTIs + NNRTI
o 2 NRTIs + boosted PI
• Started when CD4 falls
• Aim to switch off virus replication
• Taken life long, suppression >10yrs achieved
• Now problems with toxicity
84
What are the steps in viral maturation that can be targeted?
1. Fusion of HIV to host cell surface
2. HIV RNA reverse transcriptase, integrase and other viral proteins enter the host cell
3. Viral DNA is formed by reverse transcription
4. Viral DNA is transported across the nucleus and integrates into host DNA
5. New viral RNA is used as genomic RNA and to make viral proteins
6. New viral RNA and proteins move to cell surface= new immature HIV formation
7. Virus matures by protease releasing individual HIV proteins
85
What is HIV Mutation?
* HIV genome contains ~9,000 nucleotides (is an RNA gene)
* Every genome contains at least one mutation (replication has high error rate)
* A strain will become predominant if it has a selection advantage over fellow progeny
* e.g. M184V mutation results in resistance to Lamivudine, so in presence of Lamivudine the rare pop of strains with this mutation will soon predominate
* Can sequence- reverse transcriptase HIV; from nucleic acid we can infer protein so resistance mutation
86
What is HIV Cure by CCR5∆32/∆32 Stem Cell Transplantation?
• HIV needs interac with receps CCR5 or CXCR4 to enter CD4+
• Successful CD4+Tcells reconstitution at systemic level &; in gut mucosal immune system after CCR5∆32/∆32 stem cell transplantation & patient remains without an y sign of HIV infec
• During immune reconstitution process- replacement of long-lived host tissue cells with donor-derived cells indicating size of viral reservoir has been reduced over time
• Hep C- RNA virus, if can supress virus, immune system will clear it (has no latent form)- so can be cured
• Mutation in CCR5 (some of us have mutation)
• CCR5- is a co-recep needs to be binded to by HIV for it to invade cell
• CCR5 delta 32 allele freq;
o Mutation geographically determined where you live (in North Europe)
o Many of these genes come about because certain genes give survival ADV
o People with this deletion LESS likely to be infected with HIV
87
What is the current HIV 'cure'?
* HIV suppressed on antivirals
* Existing CD4 lymphocytes destroyed by conditioning
* Stem cells reconstituted with HLA-matched but delta 32 homozygous allogeneic donor
* Antiviral therapy stopped following transplantation
* Remained HIV negative (by PCR)
* HIV antibody titres have declined post bone marrow transplant (so true latency of HIV in T cells, even though affects lots of cells)
88
What is Aciclovir?
Antivirals
o For Rx of Herpes Simplex Virus (HSV) and Varicella Zoster Virus (VZV)
o Nucleoside analogue (phosphorylated by herpesvirus thymidine kinase)
89
What is Ganciclovir?
Antivirals for cytomegalovirus (CMV)
90
What is Oseltamivir and Zanamavir?
Antivirals
(neuraminidase inhibitors)- block coating of virus
o Influenza
91
What is Ribavirin?
Antivirals
| (broad spectrum of activity)- RSV, HCV and HEV
92
What are Interferons?
Antivirals
| (can be naturally immune)- Hepatitis B virus cure
93
What does a Urine Dip Test show that may support diagnosis of infection?
• WC;
o Leucocyte esteratse- enzyme made by neutrophils
o May reflect pyuria associated with UTI
o WBCs anywhere in GU tract (including the vaginal vault) will produce LE.
o +ve in patients with chlamydia infecs, urethritis, TB, bladder tumors, viral infecs, nephrolithiasis, foreign bodies & corticosteroid use
• Nitrites;
o Nitrates excreted by kidney
o Some bacteria reduce urinary nitrates to nitrites
o +ve nitrite test usually means infec
o Need over 10,000 bacteria per ml to turn the dipstick +ve (specific but not a very sensitive test).
o A -ve nitrite test doesn’t rule out a UTI; infec with non-nitrate-reducing organisms causes a -ve nitrite test.
o Nitrate- deficient diet may cause a falsely negative test in the presence of infection
o Improperly stored dipsticks are a common cause of a false-positive test for nitrites.
• RBCs;
o ‘RBC’= peroxidase activity of erythrocytes
o Myoglobin and hemoglobin also catalyze this reaction
o High doses of vitamin C inhibit this process (vit C can produce a false-negative occult blood in stool).
o A +ve dipstick for blood in absence of RBCs by microscopy = myoglobinuria or heamoglobinuria, not true hematuria
94
What are common UTI Pathogens?
• Bacterial
o Enterobacteriaciae; GI organisms, E coli also proteus sp, klebsiella sp
o Enterococci; GI organisms
o GI organisms; E.coli (gram –ve bacilli, usually found in gut), other gram –ves from gut, anaerobes also in gut but don’t generally cause UTI, enterococci (e.g. streptococci in gut) which can cause UTI,
o Staphylococci; skin organisms, S saprophyticus, (S aureus)
o (nb anaerobes, pseudomonas sp)
* Fungal- Candidia (catheter/ stents, diabetes)
* Viral- adenovirus (haemorrhagic cystitis)
95
What are Common Antibiotics for Lower UTI?
* Trimethorprim
* Nitrofurantoin
* Amoxicillin
* (Piv)mecillinam
* Fosfomycin
* (Cephalosporins, ciprofloxacin)- (don’t use these as much as high rates of C.diff infecs)
• Nitrofurantoin, pivmecillinam & fosfomycin Leeds guidelines for lower UTI (empirical)
```
Resistance in Urinary Isolates (approx.)
• amox 60 – 70%
• trimethoprim 30 – 40%
• nitrofurantoin 10 - 20%
• cefalexin 10 – 20%
• co-amox 10 – 20%
• ciprofloxacin 10 - 20%
• pivmecllinam 5-10%
• fosfomycin <5%
```
96
What is Nitrofurantoin?
* Nitrofurantoin is well absorbed after oral administration
* Serum levels remain low
* Therapeutic levels are achieved only in the urine
* UNLESS eGFR less than 45 mL/ min/ 1.73m2
* Treatment of simple, uncomplicated lower UTIs
* Development of resist¬ance is relatively rare, and nitrofurantoin is unlikely to affect bowel or vaginal flora
* It may be considered as long- term prophylaxis
* Can be given in preg¬nancy, but should be avoided at term
97
What is (Piv)mecillinam?
* Pivmecillinam is the oral pro- drug of mecil¬linam
* a penicillin that is relatively stable to bacterial beta- lactamases, including ESBLs.
* active against a range of coliform organisms, including some multi-resistant strains of E. coli, Klebsiella, Enterobacter, and Proteus
* Pseudomonas species are not susceptible
* Little activity against Gram- positive organisms such as enterococci.
* Pivmecillinam is used to treat lower UTI.
98
What are Antibiotics Suitable for Upper UTi due to E.coli?
```
• Cefuroxime
• Aztreonam
Ppiperacillin-tazobactam
• Ciprofloxacin
• Gentamicin
Cephalosporins, co-amoxiclav, ciprofloxacin….- associated with high risk of c. diff infec
```
99
What is Sepsis?
presence (probable/ definite) of infec with systemic manifestations of infec
100
What is Severe sepsis?
sepsis- induced tissue hypoperfusion or organ dysfunction (e.g. altered mental state- may be confusion)
101
What is Sepic shock?
sepsis- induced hypotension persisting despite adequate fluid resuscitation
102
What are Clinical Markers of Infection?
* These can be all markers of inflamm (SIRS- systemic inflammatory response syndrome)
* Temp can be high/ low
* HR, BP*, RR*, SaO2
* Altered mental state*
* Rigors, skin changes (e.g. mottled skin), decreased urine output
* NEWS= National Early Warning Score (4,5,6- medium risk of sepsis, above this is high risk)
• (* more important in acute)
103
What are Biochemical/ Haematological Markers of sepsis?
* WCC – neutrophils (usually rise)/lymphocytes (can go up/ down e.g. thrombocytopenia sign of infec)
* Plts
* Clotting (DIC)
* CRP (C reactive protein)- inflamm marker, tends to lag 24hrs after (non-specific marker of infec)
* Procalcitonin (calcitonin precursor)- raised in severe systemic bacterial infecs (not very raised in local infecs), won’t go up in viral/ fungal infecs or malignancy
* Renal function/liver function = maybe MOF (can be a sign of multi-organ failure, as in severe sepsis organ function damaged)
* Lactate
104
What is the epidemiology of sepsis?
• High incidence- UK Sepsis Trust 150 000 cases sepsis/year
• High mortality-3rd biggest killer after CHD and stroke
o estimates vary 10 – 50%
o UK Sepsis Trust 44 000 deaths/year
o increased mortality rates with increasing severity, age and co-morbidities
• High financial burden
105
What is the Surviving Sepsis Campaign ?
```
• International IC initiative 2002- guidelines to evaluate & treat patients in severe sepsis &septic shock
• Aim 25% reduc in mortality 2004
• Sepsis 6 (BUFALO mnemonic);
o Administer high flow oxygen O
o Give IV fluid challenges F
o Give broad spectrum antibiotics A
o Take blood cultures B
o Measure serum lactate & Hb L
o Measure accurate hourly urine output U
o (3 things to give patient &; 3 things need to take)
```
106
What is the importance of EARLY Recognition & Treatment of Sepsis?
* Longer it takes to take effective antibiotics- lower the survival
* SCC- start antimicrobial therapy within 1 hr of recognition of septic shock (& severe sepsis without septic shock)
* Start Smart then Focus Antimicrobial Stewardship Toolkit, PHE 2015- initiate prompt effective antibiotic treatment within one hour of diagnosis (or as soon as possible) in patients with severe sepsis or life-threatening infecs.
* NICE guideline 51- sepsis: the recognition, diagnosis & management of severe sepsis
* Ensure urgent assessment mechanisms in place to deliver antibiotics when any high risk criteria are met in 2ndry care (within 1 hr of meeting high risk criterion in an acute hospital setting)
107
What is NHSE CQUINs?
* Commissioning for Quality & Innovation (CQUIN) payment framework
* Enables commissioners to reward excellence by linking a proportion of English healthcare provider’s income to the achievement of local quality improvement goals
* 1st year of the CQUIN framework 2009/10- diff CQUIN schemes have been introduced since then
108
What is CQUIN 2015/16?
* Recognition & screening of sepsis
* Early treatment= effective sepsis treatment
* Early recognition & treatment of sepsis
* CQUIN part 2- antibiotics within 1 hr of ‘severe sepsis, red flag sepsis or septic shock’
109
What are common Gram +ve Organisms?
* GPC (cocci)- staphylococci, streptococci
| * GPB (bacilli)
110
What are common Gram -ve Organisms?
* GNC e.g. meningococcus, gonococcus
| * GNB
111
What is URT Flora?
```
Mouth flora/ upper RT;
• Streptococci, anaerobes (anO2), (GNC, candidia, staphylococci)
Nasopharynx- colonising flora includes;
• S pneumoniae
• H influenza (GNC)
• M catarrhalis (GNC)
• GNC, streptococci
• S aureus
• (1st 3 in list- common causes of infec, diff strains more pathogenic than others)
```
112
What are common Upper Resp Tract Infection?
• Viral
• Sore throat/ tonsillitis;
o Viral (EBV, rhino virus etc)
o Streptococci (GAS), anO2
• Sinusitis
o S pneumoniae, H influenza
o M catarrhalis
o Anaerobes (often in chronic sinusitis)
113
What are common Lower Resp Tract Infec)lions?
• Acute bronchitis- viral/’atypical’ (in presentation & diagnosis as can’t be picked up by culture)
• IE (infective exacerbation) COPD- viral, bacterial
• Pneumonia;
o Bacterial pathogens
- Strep pneumo, H influenza (GNC), M catarrhalis (GNC)
- ‘Hospital acquired’ + GNB (e.g. pseudomonas), Staph aureus
o ‘Atypicals’ e.g. mycoplasma, chlamydia, legionella
o Viruses e.g. influenza, para-influenza
114
What are examples of CNS infections?
• Sterile site
• Encephalitis (inflamm of brain)- viral (e.g. herpes simplex virus, enterovirus)
• Meningitis;
o N meningitis, S pneumoniae, H influenza, Listeria
o Neonates: group B streptococci, GNB, Listeria
o Immunosuppressed: +GNB, Listeria
o Post-op: + skin organisms (e.g. staphylococci)
o Viral organisms
• Cerebral abcesses;
o (usually 2ndry to local source of infec
o Streptococci, anaerobes
o Staph, fungal (IVDU, IE (endocarditis))
115
What are examples of GI Flora?
* GNB (enterobacteraciae- collection of gram –ve bacteria, not all gram –ves)
* Anaerobes
* Eneterococci
* Candida
* Pseudomonas spp
116
What are examples of GI Flora?
* Sterile site
* Infective endocarditis (Native Valve Endocarditis/prosthetic valve endocarditis- diff organisms depending which one)
* Intracardiac device infecs
* Graft infecs e.g. in groin
* Staphylococci, streptococci
* (GN, ‘atypical’, fungal)
117
What are Formulary B Antibacterials β-Lactams?
* Penicillins (benzylpenicillin, phenoxymethylpenicillin, fluxocloxacillin, amoxicillin, pivmecillinam)
* B-lactam/ b-lactamase inhibitor combinations (amoxicillin-clavulanic acid co-amoxiclav, pipperacilllin-tazobactam tazocin)
* Cephalosporins (cephalexin, cefuroxime, cefotaxime, ceftriaxone, ceftazidime)
118
What are Formulary B Antibacterials- non-β-lactams?
* Aminoglycosides: gentimicin
* Macrolides: ery/calri/azi thromycin
* Fosfomycin
* Glycopeptides: vancomycin, teicoplanin
* Metronidazole
* Nitrofurantoin
* Quinolones; ciprofloxacin & levofloxacin
* Tetracyclines; doxycycline
* Trimethoprim
119
What is Penicillin?
• Low toxicity (good therapeutic index- dose needed has a big diff between dose that will give you toxcitiy)
• Bactericidal
• Allergic reactions
• Cross-reaction with other β-lactams (be careful with these if patient has penicillin allergy);
o Cephalosporins (5% cross reac with these)
o Carbapenems
o (Monobactams)
120
What is Penicillin G & Penicillin V?
```
• Pen G= benzylpenicillin (iv/im)
• Pen V= phenoxymethylpenicillin (oral)
• Spectrum: narrow-spectrum
• Best used for streptococci;
o E.g. S pneumoniae (pneumococcus)
o S pyogenes (group A streptococci)
• Many anaerobes
• Some GNC e.g. Neisseria meningitides (meningococcus), (N gonorrhoeae ‘gonococcus’)
• Destroyed by β-lactamases (enzymes made by bacteria)
```
121
What is Flucloxacillin?
• Oral/IV
• Spectrum;
o Covers same things as for penicillin G but broader too
o Not destroyed by staphylococcal β-lactamse
o Can use for Staphylococci (not MRSA)
o Few GNC, many anO2, most streptococci
122
What is Amoxicillin?
• Oral/IV
• Spectrum;
o Covers same things as for pen G but is also broader
o + some gram –ve bacilli (acquired/ intrinsic resistance)
o + most enterococci (‘streptococci’)
o Streptococci, enterococci, some GNB
o Destroyed by β-lactmase (so not a good anti-staphylococcal agent)
123
What is Co-amoxiclav?
• Amoxicillin + clavulanic acid
• CA= inhibitor of β-lactamase
• Broad spectrum:
o Pen G/V e.g. streptococci
o Flucloxacillin- staphylococci (not MRSA)
o Amoxicillin e.g. most enterococci (ECOC)
o Many GNB
o Many anaerobes
o NOT ESBL- producers
• Increased risk of CDI (C difficile infec), allergic reacs
124
What is ‘Tazocin’?
* Piperacillin-tazobactam
* Piperacillin- more GNB than amoxicillin
* Tazobactam- beta lactamase inhibitor (BLI)
* Anti-pseudomonal activity
* Broad-spectrum: staphylococci (not MRSA), most streptococci & enterococci, anaerobes, pseudomonas sp, GN organisms (GNC &; GNB)
* Not effectively cross BBB (blood brain barrier)- can’t use in meningitis
* Extended spectrum beta lactimase (ESBL) – use tazocin to treat any +ve ESBL infecs
125
What are Macrolides?
• Erythromycin, clarithromycin, azithromycin
• Spectrum;
o Most gram +ve organisms (staph, strep)
o Intracellular irganisms e.g. mycoplasma pneumoniae, chlamydia/ chlamydophila, legionella sp= ‘atypical’ (as doesn’t have a cell wall that beta lactams can work on)
o Limited gram –ve
Can increase anticoagulant effect of warfarin, and increase plasma conc of carbamazepine and can increase risk of myopathy
126
What are Glycopeptides?
* Vancomycin, teicoplanin
* IV (except oral vancomycin in c diff infec (CDI))
* Gram +ve organisms
* Staphylococci, streptococci, enterococci
* Acquired resistance uncommon
* Non-β- lactam
* Vancomycin has renal toxicity so need to monitor
* Monitoring
127
What is Clindamycin?
* Po (oral)/IV
* Gram +ve organisms, anO2
* Staphylococcci, streptococci, anaerobes
* Variable acquired resistnace
* Anti-toxin action (some staphylococci &streptococci release toxins which affect tissues- can’t use normal antbiotics as would still cause the toxins to be released & cause damage)
* Good tissue penetration
* Associated with c. diff infecs (CDI)
128
What are Fluoroquinolones?
* Oral/IV
* Good absorption/ tissue penetration
* Non β-lacatm
* Associated with CDI
* Intracellular activity (in tracellular infecs)
• Ciprofloxacin= early FQ
o Gram –ves, anti-pseudomonas
o Staphylococci, covers ‘atypicals’ (as is intracellular)
o Poor streptococcal/ anO2 activity
• Levofloxacin= later FQ
o Improved gram +ve, streptococci, stypicals= ‘respiratory FQ’
o Covers less GN, pseudomonas (use earlier antibiotic)
129
What are Aminoglycosides?
* Gentamicin
* IV, IM (topical)
* Gram –ve bacilli, including pseudomonas sp
* Staphylococci (but not 1st line as doesn’t work in anaerobic envs)
* Poor streptococcal activity (but can work in synergy e.g. if used it with beta lactams)
* No anO2 activity
* Monitoring as it causes nephrotoxicity &ototoxicity
130
What is Metronidazole?
```
• Oral/ IV
• Spectrum;
o Bacteria- anaerobes
o Parasites- protozoa, some helminths
• Resistance in anaerobes is anaerobes is unusual
• S/e- Antabuse, GI, neurotoxicity
```
Reaction if taken with alcohol
131
What is the most likely cause of Intravascular catheter- associated bloodstream infection? What is the most likely cause and corresponding treatment?
o Intravascular catheter- associated bloodstream infec (CRBSI)
2. What would be the best test to confirm the diagnosis?
o Paired through-catheter & peripheral blood cultures
3. Which of these is the most likely cause?
o Coagulase –ve staphylococci (normal skin flor- access to exit site of catheter/ handling catheter if aspectic technique not used) )
4.Which if these wold be best empirical treatment (based on organism you think it is)?
o Vancomycin & gentamicin
* Coagulase –ve staphylococci (cause of most medical equip infecs)- most resistant to methicillin (including flucoxicillin)
* Vancomycin has no activity against gram –ves (so if don’t know what your treating need to make sure covered all grounds)
* Can get mixed infecs- not just 1 pathogen in lumen of line but 2
* Gentamicin can be nephrotoxic
* Look at patient’s microbiological history e.g. check if patient had MRSA
* Need to remove line from patient
132
Blood cultures grow Pseudomonas aeruginosa (gram –ve) sensitive to gentamicin, piperacillin/ tazobactam & Staphylococcus epidermidis sensitive to vancomycin. What would be best directed treatment?
Pipercillin/ tazobactam & vancomycin (vancomycin only works for gram positive)
133
What Is the best treatment for Community acquired pneumonia?
Amoxicillin/ clavulanate & clarithromycin
• Vancomycin not the best for pneumonia (there are better drugs)
• Gentamicin doesn’t penetrate well into lung tissue
• Amoxicillin/ clavulanate- doeesn’t cover the atypical causes & chest x-ray looked atypical
3. All blood cultures grow coagulase –ve staphylococci, what would you change to?
o Vancomycin alone
Note coagulase –ve means gram positive
134
What is the goal of Vaccination?
• Strategic aim:
o Selective protect of the vulnerable
o Elimination- herd immunity
o Eradication
• Programmatic aim:
o Prevent deaths
o Prevent infection, transmission (2ndry cases) & clinical cases
o Prevent cases in a certain age group
o To reduce mortality & morbidity from vaccine preventable infecs
• Diff groups of people get diff vaccines depending in their susceptibility
135
Why Immunise?
* Prevent individual disease (life-long, not just in children)
* Halt carriage & transmission= herd immunity is a side effect
* Eliminate > eradicate disease
* High coverage is operational target (get enough people immunised)
136
How Does Immunity Work?
```
Non-specific defences;
• Unbroken skin- physical barrier
• Mucous memb of gut, lung
• Acid & enzymes of gut- physiological barrier
• Non-specific metabolism/inactivation
Innate immunity;
• Complement, WBC & cytokines
Immune system;
• Immunoglobulin: initially not specific
• Learns specific IgG response
• Lays down immune memory
```
137
What is Passive Immunity?
* Passive- we’re not doing anything
* E.g. transfer from mum to unborn baby
* ‘Maternal antibodies’- can protect baby for up to a yr against illness to which mum is immune
* E.g. immunoglobulin (IG), which contains antibodies pooled together from blood of many donors, can be injected into a person who needs antibodies
* This passive immunity effective but disappears within several wks or months
* Most types of transfused blood contain antibodies
138
What is Active Immunity?
* Active immunity- long standing immunity produced by immune system in response to antigens
* These antigens can form from natural infec or vaccination
* The immune system makes antibodies to help destroy antigens
* Vaccination benefit- active immunity occurs without disease/ disease complications
* ‘Immunological memory’- persistence of protect for many yrs after natural infec/ vaccination
* Active immunity can be nature immunity in response to an illness/ vaccine induced immunity
139
What is an Antigen?
* Antigen (from microorganism)- anything that can be bound by an antibody
* Antibodies interact specifically with small parts of molecules (antigenic determinants/ epitopes)
* Antibody- made to a specific antigen & have variable constant regions, trigger range of protective effects
* Antibodies neutralise toxins/ block adhesion/ cell entry/ opsonisation/ kill via complement/ neutralise viral infectivity & prevent replication
* Diff types of antibody; IgM, IgG, IgA, IgE
140
What is the difference between primary and secondary Immune Response?
* Primary immune response develops in weeks after 1st exposure to antigen- mainly IgM antibody (I’M ill)
* 2ndry immune response faster & more powerful- mainly IgG antibody
141
How Do Antibodies Produce Immunity?
* Antibodies made from B lymphocytes
* Antigen binds non-specifically to variable region of antibody (Ig) molecule- triggers clonal expansion (bigger response)
* 1st wave of IgM produc followed by IgG production
* IgG binds tightly to antigen through simultaneous complement binding, facilitates destruction of antigen-bearing microorganism
* When infec resolved- IgG levels decline
* But 1 set of IgG producing B lymphocytes persist- have ability to recognise specific antigen= immunological memory
142
What is Passive Immunity?
• Vertical transmission of autoantibodies from mum to foetus & breastfeeding
• Injec of human immunoglobulin (Igs);
o HNIG- pooled plasma
o Specific- tetanus, botulism, hep B, rabies, varicella
143
What is Active Immunity?
* Natural infec
* Inactivated/ attenuated live organisms
* Live: MMR, BCG (against TB), Yellow fever, Varicella (act like the natural infec)
* Inactivated organisms: pertussis (whooping cough), typhoid, IPV
* Components of organisms: influenza, pneumococcal immunoglobulin
* Inactivated toxins: diphtheria
144
What is the Vaccination Theory?
• For infecs transmitted from person to person- crucial factor determining spread of infec is how many secondary cases are caused by each infectious person?
• This is the susceptible population;
o Any person not immune to a particular pathogen- susceptible
o Person may be susceptible because he/ she hasn’t encountered infec/ vaccine against it before
o Person may be susceptible because they can’t mount an immune response
o Person may be susceptible because vaccine contraindicated for that individual
145
What are Live Vaccines?
* Attenuated strains which replicate in host- attenuation means virus/ bacterium weakened to reduce virulence so can’t cause disease in healthy people
* Act like natural infec- live vaccines closest to actual infec so elicit good, strong, long-lasting immune response
* Freq of reactions decreases with number of doses- ab produced in response to live vaccine neutralises small amount of vaccine virus in subsequent vaccine dose
* Timing of vaccine reactions- occur according to time taken for virus to replicate e.g. MMR vaccine; reac to measles component (malaise, fever, rash) 1st wk after vaccine, reacs to rubella component (pain, stiffness/ joint swelling) occur 2nd wk after vaccination, reacs to mumps component (parotid swelling) occurs in 3rd wk after vaccine (although can occur up to 6 wks following vaccine)
146
What are the advantages and disadvantages of Live Vaccines?
ADV;
• Single dose usually sufficient for long-lasting immunity
• Strong immune response evoked
• Local &systemic immunity produced
Disadv;
• Potential to revert to virulence
• Contraindicated in immunosuppressed & preg patients
• Interference by viruses/vaccines & passive antibody
• Poor stability
• Potential for contamination
147
What are Inactivated Vaccines?
• Either- suspensions of whole intact killed organisms e.g. whole cell pertussis, influenza, rabies, hep A
• Or Acellualr &; sub-unit vaccines;
o Contain 1 or a few components of organism important in protection
o E.g. acellular pertussis vaccine contains 2-5 components of whole cell pertussis bacteria
o E.g. diphtheria toxoid
o E.g. Hib polysaccharide
• Freq of reactions increases with number of doses- if ab levels are good from earlier vaccination, ab binds to vaccine antigen in a subsequent dose leading to inflamm response
• Timing of vaccine reactions- generally 48hrs after vaccine
148
What are the advantages and disadvantages of Inactivated Vaccines?
```
ADV;
• Stable
• Constituents clearly defined
• Unable to cause infec
DISADV;
• Need several doses
• Local reactions common
• Adjuvant needed; keeps vaccine @ injection site, activates antigen presenting cells
• Shorter lasting immunity
```
149
What are local vs general reactions?
* Local- pain, swelling/ redness at injection site; small nodules may form at inject site
* General- fever, irritability, malaise, fatigue, headache, nausea, vomiting, diarrhoea, loss of appetite
150
What is the Routine NHS Programme?
* 2 mth: DTaP/IPV/Hib + pneumo + rota + Meningococal B
* 3 mth: DTaP/IPV/Hib + rota
* 4 mth: DTaP/IPV/Hib + pneumo + Men B
* 12 mth: Hib/Men C + MMR + pneumo + Men B
* 24 - 48 mth: annual flu
* 40 mth: dTaP/IPV + MMR
* 12 years: HPV for girls
* 14 years: Td/IPV
* 65 years: pneumo + annual flu
* 70 years: shingles
* Men C taken out from 3 months &14 yrs
• Changes in UK childhood immunisation scheldule
• Added more serogroups to pneumococcal vaccination
• Cease universal adolescent BCG
• HPV (& cervical cancer)
• New vaccines;
o Varicella/ Zostavax
o Menveo (conjugated meningococcal ACYW135)
o Men B
o Rotavirus
o Fluenz
151
What is Vaccine Effectiveness?
• After licensure, vaccine effectiveness monitored through;
o Surveillance of disease incidence
o Ascertaining vaccination status of individuals with disease
• No vaccine 100% effective &; effectiveness of each vaccine varies
• So recommend more than 1 dose & booster doses of vaccine;
o E.g. about 90% of people given MMR vaccine will seroconvert after 1 dose of vaccine
o A 2nd dose recommended so those not protected after 1st dose have a 2nd opportunity to make antibodies
152
What is the Chain of Infection?
* Pathogenic organism- of sufficient virulence & in adequate numbers to cause disease
* Reservoir/ source that allows organism to survive & multiply
* Mode of exit from source
* Mode of transmission from source to host
* Portal of entry through which pathogen can enter host
* Susceptible (i.e. non-immune) host
153
What is Infection Prevention & Control?
Activities undertaken with the aim of braking chain of infec;
• Eliminate pathogenic organism;
o Environmental cleaning & decontamination; H2O2 room decontamination, spillage management, laundry (appropriate handling)
o Equipment decontamination; sterilisation, disinfection
o Antisepsis; surgical skin prep, MRSA decolonisation
o Antibiotic prophylaxis; perioperative, post-exposure
• Remove source/ reservoir;
o Hand hygiene
o Environmental cleaning & decontamination
• Minimise transmission;
o Hand hygiene
o Personal protective equip (PPE) for healthcare workers; aprons, gloves, masks
o Equip decontam; surgical instruments, stethoscopes, blood pressure monitors, USS probes etc
o Source & protective isolation
o Use of disposable equip; syringes, needles etc
• Eliminate exit & entry
• Reduce susceptibility to infec
154
What is Semmelweis?
2 free obstetric clinics, admitted alternate days. 1st clinic- maternal mortality, puerperal fever (group A strep) (10%), 2nd clinic (<4%). 1st clinic by medical students (who also attended autopsies), 2nd by midwifery students. Handwashing with chlorinated lime after autopsies introduces (pre: 18.3%, post: 2.2%)
155
What do we carry on our hands? (2 types)
Resident Bacteria (goof bacteria)
• Deep seated
• Difficult to remove
• Aid in protecting us from colonisation with harmful species
• Are only removed when undertaking surgical/ aseptic procedure (reducing risk of contamination when inserting invasive devices/ performing surgery)
Transient Bacteria
• Easily picked up & transferred
• Easily removed
• Important cause of Healthcare Associated Infecs
156
What is Sterilisation?
• Complete killing/ removal of all types of microoganisms;
o Bacteria; vegetative (in a state ready to multiply), spores (certain species can form these e.g. Clostridium tetani, C.difficile etc)
o Viruses
o Fungi
o Mycobacteria
• Sterilisation methods;
o Heat; moist, dry
o Chemical; by gas, liquid
o Filtration
o Ionising radiation; used for single use disposable equipment
157
What is Sterilisation by Heat?
Moist heat;
• Autoclave; deliver steam under high pressure, specific pressure &; temp cycles to kill what sort of organism required
Dry heat;
• Oven; controlled temp cycles (higher temps), 160° for 2 hrs or 170° for 1 hr
158
What is Disinfection?
Disinfection
• Removal/ destruc of sufficient numbers of potentially harmful micro-organisms to make an item safe to use
• Antisepsis- disinfection applied to damaged skin/ living tissues, needs a disinfectant with minimal toxicity
• Almost always achieved by use of chemical disinfectants (sterilisation is done by heat)
• Properties to consider:
o Effects on micro-organisms (diff agents diff effects on microoganisms)- antimicrobial spectrum, sporicidality (if can affect spores)
o Chemical properties- shelf life, in-use concentration, compatibility with other chemicals
o Physical effects- corrosiveness
o Harmful effects- irritant potential, toxicity
159
What is the infection risk of Surgical Instrument Reprocessing?
* Risk of infec- high
* Physical properties- metal construction, paper/cloth packaging
* Decontamination level- sterilisation
* Decontamination method- moist heat
160
What is the infection risk of Flexible Endoscope?
* Risk of infec- high
* Physical properties- metal/ plastic construction, fragile, sensitive aprts
* Decontamination level- high level disinfection
* Decontamination method- chemical (not destroyed by heat); several alternative agents, delivered via ‘washer-disinfector’ (ensuyre chemical goes down all channels)
161
What is the infection risk of Syringe Needle ?
* Risk of infec- high
* Physical properties- plastic/ metal construction, paper packaging
* Deconatmination level- sterilisation (as going through skin)
* Decontamination method- ϒ- irradiation pre-use, disposal after use (risk of transmission)
162
What is the infection risk of Central Venous Catheter (CVC) Insertion Site?
* Physical properties- living tissue
* Decontamination level- disinfection (antisepsis- disinfect skin)
* Decontamination method (2% chlrohexidine in 70% isopropyl alcohol)
163
What is the infection risk of Surgeon’s Hands ?
* Physical properties- living tissue
* Decontamination level- washing
* Decontamination method- surgical scrub
164
What are the General Principles of Investigating Infections?
• Investigations ADD to clinical picture do not REPLACE it
• Each test asks a specific Q;
o What is causing the infec &; what can I use to treat it?
o Is this person at risk of developing an infec?
o Is this infec?
• No test is infallible- each has +ve & -ve error rate
• If test doesn’t ass to management/ prognosis- DON’T DO IT
• Remember HIV testing- acute medical admission, new GP registration
• Local vs General
• Local sampling;
o From source of infec
o Assist with diagnosis
o What bug causing infec, what drug to treat patient with
• General (systemic) sampling (as part of investigation of sepsis);
o Blood cultures
o FBC, U&Es, LFTs, clotting, CRP (how patient handling infec)
165
What is Meningitis? How would you investigate the cause?
• Inflammation of meninges
• Caused by viruses, bacteria, mycobacteria, fungi, parasites (need to work out which one causing meningitis so can guide treatment)
• Lumbar puncture (LP)- collect cerebrospinal fluid (CSF
• Other tests;
o Blood cultures (2 sets)
o Blood for bacterial PCR (targeted PCR- S. pneumoniae &; N. meningitides 2 biggest causes of meningitis)
o FBC, clotting, U&Es, LFTs, glucose, CRP
o Immunosuppressed: CSF crytococcal antigen (fungal), TB culture/ PCR
• Can also do gram & culture of CSF- give more of idea of what pathogen is
Viral, fungal and TB - mainly lymphocytes and low protein
Bacterial-mainly polymorphs, and More protein, turbid appearance, increase WBC
Viral decreased WBCs, >0.6 glucose
Bacterial, fungal and TB <0.4 glucose
166
What is Encephalitis? How would you investigate the cause?
* Inflammation of brain- usually viral (Herpes viruses)
| * CSF requesting Viral PCR specifically (doesn’t get done routine)
167
What is a Brain Abscess? How would you investigate the cause?
* Wide aetiology: bacterial, mycobacterial, fungal, parasitic
* History (patient factors) can narrow down- ear, sinuses, blood, post-op etc
* Lumbar puncture discouraged (rarely +ve, high risk as high pressure- can cause brain damage if lower pressure down below by a lumbar puncture)
* Local sampling: pus- surgical biopsy/ drainage= Gram, culture, sensitivity (PCR- look for bacterial remnants)
* Blood cultures
168
What is Acute Otitis Media? How would you investigate the cause?
* Inflamm of middle ear usually caused by viruses (can get bacterial 2ndry infec)
* Samll & contained so difficult to get sampling- need to wait for ear drumb to perforate to get pus sample, but then would be mixed with other organisms in ear canal (bear this in mind when interpreting result)
* Clinical diagnosis, viral & bacterial, send pus if ear drum perforated
169
What is Acute Otitis Externa ? How would you investigate the cause?
• Ear swab: determine cause (bact., fungal etc) &sensitivity
170
What is Sinusitis? How would you investigate the cause?
* Inflamm of sinus lining
* Majority viral
* 2ndry bacterial infec
* Caused by upper resp flora (difficult to see what’s normal flora & what’s causing infec)
* Sample in all but severe cases is unhelpful
* Severe cases; pus from operative sinus lavage, FBC, blood cultures (if on severe end of scale & become septic then do blood cultures) etc
171
What is Pharynitis? How would you investigate the cause?
* Pus/ exudate on tonsil/ back of throat
* Majority viral
* Only send throat swabs if evidence bacterial infec (as viral self-limiting)- looking for B-Naem Streps
* Discount normal flora as contamination
* Additional tests; EBV serology, Diphtheria swab, pus if Quinsy abscess (peritonsillar abscess)
172
What is Influenza ? How would you investigate the cause?
• Seasonal (autumn, winter), sporadic vs epidemic, highly transmissible
• Not necessary to test everyone (some just need symptomatic relief), just test;
o Those who may need treatment e.g. immunosuppressed
o Those at risk of transmitting e.g. care home resident
• Nose/ throat swabs
• Immunofluorescence vs. PCR;
o Used to do immunofluorescence but time consuming
o So now use PCR; has sensitivity >90% & specificity 99%, fast, scalable, cost
173
What is Pneumonia ? How would you investigate the cause?
```
• Pneumonia (e.g. from bacterial infecs)- clinical diagnosis based on respiratory symptoms, signs & CXR changes (microbiology not as helpful)
• Severity assessment CAP= CURB 65 score (confusion, urea, RR, age >65) out of 45;
o CRP (inflamm marker to see if viral/ bacterial infec) may help guide diagnosis & antibiotic need
o Low score (0-1): no investigation needed (don’t do microbiology)
o Mod-severe (2-5): sputum, blood cultures (if systemically unwell), atypical screen (urine for Legionella antigen, nose/throat swab for mycoplasma, might include serum)
```
174
What is Pulmonary Tuberculosis? How would you investigate the cause?
• Disease which requires EXPOSURE (inhale bacilli which can remain dormant) then REACTIVATION (e.g. if immunity wanes) at later stage in life (pulmonary symptoms)
• Exposure testing;
o Mantoux (inject tuberculin in skin to determin presence of infec)
o IGRA (interferon G releasing assay) (QuantiFERON-TB, T-Spot TB)- blood tests; take white cells out- expose them to TB extracts- look for white cells triggering off- shows white cell have memory &; been exposed in the past (may have latent TB)
o Rely on intact immune system
• Pulmonary symptoms;
o 3 sputum samples
o Microscopy &; culture (for 8 wks- to grow TB)
o PCR- Rapid, costly, lower sensitivity ( directly from tissue/ sputum/ culture to try to i.d. sputum (still not as good as culture in terms of sensitivity))
175
How would you investigate the causes of atypical respiratory infections?
• Consider in immunosuppressed;
o Haemato-Oncology- on chemotherapy, solid organ transplant
o Steroids, diabetes, CKD, underlying disease (HIV, congenital, liver etc)
o Travel
• Viral (e.g. RSV, CMV)- viral PCR
• Fungal (e.g. Aspergillus)- culture, Aspergillus antigen
• Aspergillus prevalent in immunosuppressed
• Pneumocystis (atypical pneumonia)- PCP PCR
• Not looked for routinely, need to guide lab with history
• Usually best investigates by deep resp samples (BAL)
176
What are Impetigo, Erysipelas and Cellulitis ? How would you investigate the causes?
localised Skin & Skin Structure Infections
• Localised- blister- better rate to i.d. pathogen
• Localised tend to get treated empirically
• Wound swabs; not helpful from intact skin, send blister fluid/ abscess pus
• Needle aspirates from cellulitis: poor- only determine pathogen in 10-30% cases
• Blood cultures: only +ve in most severe 5%- send if sepsis
177
What is Necrotising Fasciitis ? How would you investigate the cause?
* Eats through tissue
* Rapidly spreading synergistic infec
* Surgical Emergency, high mortality
* Debrided tissue/ Pus-M, C & S
* Want pus & tissue sample from debridment (from clean area- to see if surgeon have removed all bacteria)
* Blood cultures (2 sets)
* Bloods: FBC, U&E’s, LFT’s, CRP
178
What is Diabetic Foot Infection ? How would you investigate the cause?
* Can lead to peripheral neuropathy, patient can’t feel when they’re being damaged
* Have impaired circulation
* Ulcers get colonised with skin flora (get skin &enteric flora- hard to find out which just flora & which causing the infec)
* Non-infected wounds/ ulcers; smelly weeping exudate not evidence of infec- do NOT send swabs
* Mild infec; wound swabs (sensitivity 49%, specificity 62%)
* Mod/ Severe (deep) infection; debride wound (get rid of surface tissue & flora to get to healthy tissue not invaded by bacteria) then collect clean bone or tissue sample (affect bone)- specialist
* Sample tell you WHAT causing infec not whetehr they have infec or not
179
What is a UTI? How would you investigate the cause?
UTI- LOWER (CYSTITIS) & UPPER (PYELONEPHRITIS)
• Clinical Diagnosis supported by Microbiology
• Answers question (urine sample)- what is causing this UTI & how should I treat it but not does this patient have a UTI
• Bacterial growth & sensitivities- antibiotic sensitivities (tell you what to treat)
• If dysuria & frequency probability of UTI >90%
• Urine sample: WBC, RBC, epithelial cells, bacterial growth, sensitivities
• Interpretation:
o Kass Criteria: threshold for ‘significant bacteriuria’ (signif bacteria in urine to have UTI- but doesn’t work as well as symptomatic bacteruria- can have lots of bacteria in urine causing no harm)
o Automated analysers: microscopy to predict culture positivity
o How the urine is collected: MSU, CSU, Bag, SPA
180
What is Prostatitis ? How would you investigate the cause?
UTI
• 50% of patients with recurrent UTI’s & 90% of febrile UTI’s have prostatitis
• Urine mainstay of investigation (post prostatic massage)
• Use urine testing
181
What is Epididymo-Orchitis ? How would you investigate the cause?
* 2 main aeitiologies: enteric/ UTI or STI
* Urine- sent for cultures AND sent for Chlamydia & Gonorrhoea NAAT (PCR)
* If severe infec: bloods, blood cultures, USS +/- drainage
182
What is Infectious Diarrhoea ? How would you investigate the cause?
• Wide range of pathogens:
o Viruses (norovirus, rotavirus)
o Bacteria (Campylobacter, Salmonella, Shigella, E coli 0157, Vibrio)
o Parasites (Cryptospordium, Giardia, foreign travel)
o C. difficile infection (CDI)
• Lab needs guiding with clinical details/ risk factors e.g. if infectious diarrhoea &; patients hospitalised may look for C. diff, if abroad- parasites, if nursing home- norovirus (need to guide lab as to what your testing for)
• Majority of viral and bacterial disease is self limiting
• Stool Sample
• Why sample: treatment, Public Health, Avoid transmission (e.g. put people in isolation)
• Other investigations:
o Parasites- 1 stool not enough (3 collected at diff times) improves pick up chance of microorganism)
o Bloods: FBC, clotting, U&E’s, LFT’s, CRP
o Blood Cultures
o Abdominal Imaging: plane film or CT
183
What is Helicobacter pylori ? How would you investigate the cause?
H.pylori- infec of stomach lining
Used to guide antibiotic treatment;
• H. pylori antibody test (sens 92%, spec. 83%)- insensitive, doesn't distinguish active from past infection
• H. pylori stool Antigen (sens 95%, spec 94%)- simple, non-invasive, inexpensive
• Urea Breath test (sens 88-95%, spec 95-100%)- expensive, pt experience, gold standard for test of cure (uses bacteria’s ability to break down radiolabelled urea- detect radiolabelled carbon in breath)
• Biopsy Urease test (sens 90-95%, spec 95-100%)- invasive, cross reactions
• Stop PPI’s before testing
184
What is a Liver Abscess ? How would you investigate the cause?
* Pyogenic (bacterial), Hydatid (worm) or Amoebic (parasite)- history to guide aetiology
* Pus sample (if safe to drain- hyaditid not safe as if rupture worms get into abdominal cavity)- put needle in & drain it
* Stool for OCP (eggs/ cysts in stool)
* Blood Cultures
* FBC, U&;E’s, LFT’s, CRP
* Hydatid serology
* Imaging: USS/CT
185
What is Cholangitis/ Cholecystitis ? How would you investigate the cause?
* Cholangitis- inflamm of bile ducts & gall bladder
* Bloods: FBC, U&E’s, LFT’s, Clotting, amylase
* Blood Cultures (to try to get causative pathogen)
* Imaging: USS or CT
* Bile fluid or Pus (if aspirated/drained)
186
What is Diverticulitis ? How would you investigate the cause?
* Outpouching in colon- can get inflamed (most likely to be inflamm rather than infective process in uncomplicated, but do in complicated)
* Uncomplicated vs. complicated
* Complicated= abscess, fistula, perforation, obstruction
* Pus from abscess
* Blood Cultures if systemically unwell
* Bloods: FBC, U&E’s, LFT’s, Clotting, amylase
* Imaging: CT
187
What is Endocarditis ? How would you investigate the cause?
• Endocarditis- blood rushes past heart valves which are infected, vegitations release bacteria in blood stream
• Blood cultures fundamental to management (96% positivity)
• Take 3 sets of Blood Cultures at diff times during the 1st 24 hours in all patients with suspected endocarditis (as may not be enough bacteria at 1 point in the day to pick up)
• Other investigations:
o Echocardiography (imaging heart valves- USS)
Trans-Thoracic Echo TTE (sens. <60%; spec 98%)- looking across chest wall at heart valves but not great pick up rate
Trans-Oesophageal Echo TOE ( sens. and spec. of >94%)- camera down oesophagus, higher sensitivity & specificity
o TOE should always be done for suspected PVE
o FBC, CRP, U&E’s, LFT’s
o Serology (if answer not in blood cultures) for Bartonella, Chlamydia, Coxiella, Brucella
o Valve tissue if valve replaced: M,C and S and PCR
• Need to correctly i.d. organism as patient may be getting 6 wks of IV antibiotics
188
What is Vascular Graft Infections ? How would you investigate the cause?
```
• Vasc graft infec- eroded through native vessel wall, graft can be walled off from circulation
• Take 3 sets of Blood Cultures at different times during the first 24 hours in all patients with suspected
• Lower culture positivity rate
• than endocarditis
• Other investigations:
o Imaging: CT, PET, WBC scan-
o fluid around graft, fistulae
o Tissue/fluid from around graft-
o for culture or PCR
```
189
What is Syphilis? How would you investigate the cause?
• Ulceration around genital area
• Early (Primary & Secondary), Latent, Late (Tertiary- gummatous, neuro, cardiovacular) and Congenital
• Testing not very sensitive/ specific
• Detection by PCR (superseded dark ground microscopy)- easier to diagnose
• Serology (strong during acute phase, less specific in later stage):
o Screening test including IgM (& general antibody) in (acute) Primary infection
o Treponemal Specific Antibody (eg. TPPH, TPHA) (non-specific?)
o Non-Treponemal Specific Antibody (eg. VDRL, RPR)
Expressed as dilution (1:16; 1:32 etc.)
If can detect in more dilute- strongly +ve
• Syphilis investigation- diff stages, sensitivity in earlier stages better than in late stages
190
What is Viral Hepatitis ? How would you investigate the cause?
* Hep- based on Serology +/- PCR
* Serology comprises ANTIGEN and ANTIBODY detection
* ANTIGEN- components of organism (if can detect this- is active infec, if don’t detect doesn’t mean not there)
* ANTIBODY- body's immune response to organisms (acute IgM and chronic IgG) (give idea of immune system)
* IgG- had infec in past/ been vaccinated
* PCR detects DNA or RNA from living or dead organisms
* Usually presence of DNA/RNA suggests active infection
191
What is Hepatitis A ? How would you investigate the cause?
* Incubation period (15-45 days), then up in stool (as feoco-oral spread), then acute disease (2-12wks-jaundice symptoms), convalescence and recovery >3mnths
* Body develops immune response, happens immediately (IgM rise which then tails off, then rise in IgG)- mainly serology
192
What is Hepatitis B ? How would you investigate the cause?
• Is antigen present; yes= acute or chronic infec
• Diff markers; surface antigen tells you if replication/virus in circ
• Then develop antibodies to the diff components
• Can have acute infect that clears
Can then develop chronic active infec
Infection then incubation for 2wks-3mnths HBsAg and HBeAg snd some symptoms then approx 3-6mnths anti HBC which increases and HBS which increases slower, then anti HBE and late anti HBc IgM which decreases after approx 6-12mnths the other last approx.29yrs whereby anti HBe starts decreasing
193
What is Hepatitis C ? How would you investigate the cause?
• Look for in blood- look for antibody again, rise with acute infec.
• Body can get rid of infec or you develop chronic carrier state
But antibody persists stays lifelong regardless of this so need to test to see if ongoing chronic infec (&are a carrier) or if test –ve shows they have cleared infec from their system
Initially in first month sharp increase and decrease of alanine transaminase and increase in anti-HCV.
194
What is Antimicrobial Stewardship?
• NICE- healthcare-system-wide approach to promoting &; monitoring judicious use of antimicrobials to preserve their future effectivness
• Antimicrobial stewardship;
o Inter-professional effort across care
o Timely optimal selection, dose & duration of anti-microbial
o For best clinical outcome of treatment/ infec prevention
o Minimal toxicity to patient
o Minimal impact on resistance & other ecological adverse events e.g. C. difficile
• 4 goals; improve patient outcomes, improve patient safety (e.g. C.diff), reduce resistance, reduce costs
195
What is Spsis? What are the red flags?
```
• 44k deaths UK/yr, 11k preventable
• National incentive scheme (CQUIN) for 2yr- screening & rapid AB if needed
• Red flags & infec;
o SBP <90mmHg
o Lactate 2 or more
o HR >130/min
o Resp >25/min
o Need O2 for SpO2 >91%
o No urine in 24h or >0.5ml/kg/hr
o Response only to voice/ pain
o Non blanching rash/ mottled skin
```
1. Administer high flow oxygen
2. Take blood cultures
3. Give broad spec antibiotics
4. Give IV fluid challenges
5. Measure serum lactate & Hb
6. Measure accuratly hrly urine ouytpuit
7. (Infec source control)
• In order to ensure they happen- sepsis 6 pack
• NNT= 5 for survival where implimented
• ICNARC: 47% mortality ↓ with FULL sepsis 6 & 15% ↓ risk of death with timely AB, 4.5% ↓ mortality in 1st yr of sepsis CQUIN
196
What is the Strategy of Antibiotic Use?
• Clinical histroy & examination
1. Empiric therapy- based on; predicted susceptibility of likely pathogens & local antimicrobial policies (know little about bacterial infec)
2. Targeted therapy- based on; perdicted susceptibility of infecting organisms & local antimicrobial policies
3. Susceptibility- guided therapies- based on; susceptibility testing results (after gotton lab results)
197
What is the 90:60 Rule (Rex)?
* The ’90-60 rule’: the range of correlations between susceptibility &; outcome in studies of bacterial infecs
* Infecs due to SUSCEPTIBLE isolates respond to thewrapy 90% of the time
* Infecs due to RESISTANT isolates respond 60% of the time anyway (patient will get better)
198
What is the single BIGGEST contributor to mortality?
Inadequate Empirical Therapy (single BIGGEST contributor to mortality)
• What pateint had before
• If MRSA carrier or have extended spec beta lactamases, or Ca RE- worries
199
What Should Prescribers CONSIDER When Prescribing In Acute Practise?
* Is this a BACTERIAL infec that NEEDS antibiotic treatment? (could it be viral/ fungal)
* Patient have any co-morbidities/ history making them susceptible to bacterial infec (e.g. diabetes, immunosuppression, preg)?
* Had this infec before? Have any previous results?
* Can I wait for lab resultys to return before therapy?
What can be the potential adverse outcome of the infection?
E.g: Chest infection=pneumonia
Sore throat=Quinsy
Otitis media=Mastoiditis
200
What is Staph aureus treated with?
o Flucloxacillin- Staph aureus (not MRSA)
201
What is Strep pyogenes treated with?
o Benzylpenicillin- Strep pyogenes
202
What do Cephalosporins treat?
o Cephalosporins (caution in elderly)- Gram –ve
203
What does Metronidazole treat?
o Metronidazole- anaerobes
204
What does Vancomycin treat?
Vancomycin- gram +ves (MRSA)
205
What does Meropenem treat?
Meropenem- most-clinically relevant bacteria
206
What does Colistin treat?
o Colistin- last option for multi-resistant gram –ves (can cause nephotoxicity)
207
How do you choose which antibiotic to use?
* Depnds on infec (size & penetration)
* Allergy
* Prevalence of bacteria in pop
* Narrow spec against suspected organism
* Keep commensal pop (e.g. gut flora)
* Previous therapy
* Drug combos or montherapy (single therapy)? Affect resisatnce?
* Target spectrums e.g. cephalosporin & metronidazole
* Synergy (1+1=3) e.g. B-lactasms & aminoglycosides
* Antagonism
* Fusidate & fluclox
Selcting Route of Antibiotics
• ORAL unless sepsis or deep seated infecs (endocarditis, meningitis, osteomyeleitis etc) or patient vomiting
• Severity of infec (sick patients have variable absorption e.g. ciprofloxacin orally 85% absorbed, but sick 50%)
• Compliance/ adherence probs;
o Intolerant (e.g. vomit) e.g. can use metronidazole rectally
o TB with intramuscular
o Side effects e.g. diarrhoea with oral (60% of antibiotics associated diarrhoea is non-CDI)
208
What are Pharmacokinetic Considerations of antibiotics?
• Important determinant of in vivo efficacy is concentartion at site opf action
• CSF;
o B-lactams- good availability in presence of inflamm
o Aminoglycosides & vancomycin- poor availability (can give directly into site needed- intrathecally)
• Urine;
o Trimethroprim & B-lactams- good availability
o Macrolides- poor availability
209
What are Pharmacodynamic Considerations of antibiotics?
Concentration dependant
• Trying to get drug conc to exceed min inhibitory conc
• Administered intermittently to achieve high peaks – aminoglycosides
• Give 1 big dose, rather than continuous doses = better in terms of nephrotoxicity
• E.g. gentamycin- can give big dose once a day
• Main determinant of bacterial killing is the factor by which concentration exceeds MIC
• Trying to get concentration of drug to exceed inhibitory effect
Time Dependant
• Can give best effect by continous infusions but not practical on wards so give in fusions 3 times a day
• Main determinant of killing is amount of time for which antibiotic concentration exceeds MIC
• Administered frequently to maintain high level – B-lactams
• Get best effect by using continual effusions, not practical on wards (tend to give 3 or 4 times a day instead) but is okay on ICU
Total dose give in 24hrs
210
What is antibiotic combination therapy? Why is it used?
Reasons to combine antibiotics
• Increase efficacy
o Synergistic combination may improve outcome
B-lactam and aminoglycoside in streptococcal endocarditis
• To provide adequately broad spectrum
o Single agent may not cover all required organisms
Polymicrobial infection
Empiric treatment of sepsis
Gentamicin given one off because most rapidly acting antibiotic
• To reduce resistance
o Organisms would need to develop to multiple agents simultaneously
Anti-tuberculous chemotherapy
211
What is Penicillin allergy?
* Type 1 (IgE), <1 hour (comes on quickly)
* Frequency 1-10%
* Anaphylaxis 0.01-0.05% - very rare, vast overestimate of penicillin allergy
* Cause: beta-lactam ring
* Other allergies = 3x increase
* Vastly over-estimated
* Increased risk of carriage of MDR organisms e.g. MRSA, VRE
* Poorer infection outcomes and more side-effects from treatment as fewer treatment options – important to take good accurate allergy information (what happened, how long ago)
212
What is Cephalosporin allergy?
• Frequency: 0.05-6.5% with both
o 1st generation OR 4.8 of allergy if known penicillin allergy, 2nd generation OR 1.1 (cefuroxime), 3rd generation OR 0.5
• Cause: side chain
213
What is Carbapenem allergy?
* Meropenem = very low = 0.01%
| * Aztreonam – probably safe
214
What are consideration of antibiotic prescribing in Pregnenacy?
• Risk of teratogenesis is main concern. Only use drugs in pregnancy where benefit outweighs risk
• Penicillins, cephalosporins and erythromycin are thought to be the safest, and have most data in pregnancy and breast feeding
• always send samples for C&S to guide therapy and avoid unnecessary drugs
• guidelines exist to guide treatment
o bacteruria in pregnancy is always treated as linked to prematurity of birth
215
What are the considerations of Absorpition &Bioavailability of antibiotic prescribing?
* Bioavaliability- amount of drug absorbed
* Most antibiotics are well absorbed so oral route is preferable
* Gentamicin given by injection, erythromycin not oral
216
What are the considerations of Distribution- and Protien Binding of antibiotic prescribing?
* If have very low protien (albumin levels) tend to excrete vancomycin more than normal so need to give bigger doses
* bound drug cannot enter tissue
* protein + drug =protein-complex (equilibrium)
* albumin is basic and binds: acidic (penicillins and cephalosporins) and neutral (tetracyclines and sulphonamides)
* alpha-1 acid glycoprotein is acidic and binds basic macrolides, trimethoprim, metronidazole, clindamycin
* any change in plasma proteins will affect equilibrium and release more free drug, e.g. malnutrition, sepsis etc.
* Low protein changes equilibrium – low albumin levels = tend to excrete vancomycin more quickly than normal, so need higher dose
217
What are the considerations of dosage in antibiotic prescribing?
Dose of Antibiotic
• Nitrofuratoin- cut off based on immune system
• BNF guidance on how to adjust dose depending on renal clearance
• Always give normal loading dose & then reduce
• Lab results always based on 70kg white perosn- so may need to do calcs to adjust this e.g. if patient weighs more
• site of infection
• based on weight – gentamicin
• based on age
o nitrofurantoin – probably doesn’t work in elderly CrCl < 35/min
• Hepatic function
• Rifampicin and fusidate excrete in bile – accumulation in obstruction
• 4 – quinolones linked to necrotic hepatitis
• renal impairment
o always give normal loading dose and then reduce
o eGFR based on 70kg white person, so not true reading
218
What are the considerations of antibiotic prescribing in obesity?
```
Antimicrobial dosing in obesity
• USA
• >30% obese (BMI>30)
• 1 in 20 morbidly obese (BMI > 40)
• adipose tissue secretes cytokines
• obesity is an independent risk factor for surgical site infection, standard dosing may lead to under dosing
• may need bigger doses
```
Obesity on ADME
• Absorption – no difference
• Distribution:
o Fat accounts for 5% of CO (20-30ml/min/100g tissue)
o Hydrophilic drugs shouldn’t be affected
o Albumin bound drugs unaffected
• Metabolism – no information
• Excretion – probably increased (based on obese kidney donors)
219
What are the considerations of Biofilms on Catheters &; Prostheses?
* bacteria on outside killed
* bacteria on inside of biofilms tend to be dormant so antibiotics don’t tend to have effect on them
* Antibiotics act mainly during cell division, so needs to active cell
* Ab won’t affect sleeping cells
220
Why de-escalate?
• Reduce risk of antibiotic resistant infections
• Less nephrotoxicity
• Broad spectrum antibiotic eradicate commensal organisms
• Overgrowth of resistant organisms e.g. MRSA colonisation with quinolones
• Oral or vaginal candidiasis
• Pseudomembranous colitis from C. difficile toxin – linked to broad spectrum antibiotics
o Any prolonged broad spectrum antibiotics, especially in elderly or immunosuppressed patients
o Mortality at 28 days in 1 in 5 and at 3 months in 1 in 3
No infection = no antibiotics
Hand washing important to reduce spread of infections
Without antibiotics won’t be able to do operations, give chemotherapy etc.
221
IV to Oral Switch- Why Do it?
```
IV to Oral Switch- Why Do it?
• Apyrxical, Clinically improving, (ACED mneunomic)
• Decreases length of stay by 2-4 days
• Decreases device related infection risk
• Should be based on clinical indicators
o No continued signs of sepsis – clinically well
Temp > 38 or <36 - apyrexia
Bradycardia
Tachypnoea
WCC
o Low or decreasing CRP
o Improving generally
o Able to take oral medication
• Some infections require long courses of IV therapy – have specialist guidelines
o Osteomyelitis
o Liver abscess
o Meningitis
o Bacteraemia
o CF
o Endocarditis
o Infections in immunocompromised
Reassessment of antibiotics at 3 days
```
222
What is the duration of antibiotic prescribing?
• Don’t give too many antibiotics to patient in the first place
• Dependent on nature of infection
• Long enough to kill
• Short enough to prevent antibiotic resistance
• UTI’s 3 days women, 7 days men
• Upper respiratory days
• Osteomyelitis – 6 weeks
• TB – 6-9 months
• Complete course
o Debatable (apart from strep throat infections)
o Many patients don’t – if don’t finish give back to doctor to get rid of them
o Probably increases resistance
223
What are Antimicrobials with Narrow Theraputic Spectrums?
Antimicrobials with Narrow Theraputic Spectrums
• Narrow spectrum of theraputic use
Narrow spectrum of therapeutic use
• Too low – sub-therapeutic
• Too high – toxic (nephrotoxicity, ototoxicity – hearing or balance problems)
Examples
• Aminoglycosides e.g. gentamicin, amikacin, tobramycin
o 1 day doses due to nephrotoxicity
• Glycopeptides e.g. vancomycin, teicoplanin
Once daily aminoglycoside
• Standard dose 5-7 mg/kg
• Adjust dosing interval rather than dose
• Still use 1mg/kg 12h for endocarditis, aim for trough of <1mg/L and peak 3-5mg/L
Vancomycin
• Trough level only needed
• 10-20mg/L (15-20 for deep-seating infections)
224
What is Antimicrobial Prophylaxis?
• aim to prevent infection by suspected organisms
• max dose at time of incision or procedure (30-60 mins)
• pre-operative dose only usually needed
• repeat every 2 half-lives (IDSA)
• Number of people needed to be treated to see AB prophylaxis effects
o Colorectal surgery 4 (wound infection and abscesses)
o Small bowel surgery 5 (wound infection)
o Hip replacement 42 (SSI hip) – AB prophylaxis doesn’t have much effect
• Long prophylactic courses encourage resistance &; s/e
• Narrow spectrum agent
• Nearly always Staph aureus cover (MRSA risk)
• Topic colonisation
• Experience of surgeon, length of surgery, theatres environment, prosthesis and patient factors affect SSI rates as much as AB prophylaxis
225
What is the Ideal Time to Give SSI Prophylaxis ?
* At time of incision- smallest risk
* Give so that it is in patient before incision or application of tourniquet, bolus better
* Clean surgery involving placement of a prosthesis or implant, clean contaminated surgery, contaminated surgery: one dose of surgical prophylaxis within 60 minutes before knife to skin
226
What are the contraindications for quinolones?
• Fluoroquinolones – lower seizure thresholds in people with epilepsy, arthropathies in children and growing adults (ruptured tendons)
227
What is the contraindications for ceftriaxone?
neonates with jaundice as can displace bilirubin from albumin
228
What is the contraindications for tetracyclines?
under 12 years can stain teeth
229
Which disorder can only be given select antimicrobials?
• Myastehnia gravis
230
What antibiotics should people with glucose-6-phosphate deficiency avoid?
sulphonamides and nitrofurantoin
231
What can aminoglycoside result in?
nephrotoxicity
232
What can vancomycin result in?
nephrotoxicity
233
What can chloramphenicol result in?
bone marrow depression i.e aplastic anaemia
234
What can co-amoxiclav result in?
cholestatic jaundice increases AST/ALT/ alkaline phosphatase
235
What can daptomycin result in?
increased risk of myopathy/ rhabdomyolysis (increased creatinine kinase)
236
What can linezolid result in?
myelosupression- i.e anaemia and leucopenia and thrombocytopenia
