Micro Flashcards
Decrease abx peak concentration
Reduced gut absorption
Increased Vd
Reduced penetration to site of action
Increase Abx peak concentration
Reduced protein binding
Reduced clearance mechanism
Increase Abx t 1/2
Decreased renal or hepatic clearance
Decreased overall metabolism eg hypothermia
Decrease Abx t1/2
RRT
INCREASED hepatic clearance
Increased glomerular filtration
Increased drug metabolism
Ways that critical illness can change pharmacokinetics and dynamics of Abx
Enhanced organ toxicity due to poor clearance and increased risk of damage to organs directly
How does shock affect pharmacokinetics and dynamics of Abx
Increased Vd
Decreased bioavailability of basic drugs (due to increase in alpha 1 glycoproteins)
Increased penetration of formerly impenetratable tissue eg meningitis
Impaired hepatic metabolism due to inhibited cyp 450
In renal failure you would..... For Beta lactams Carbapebems Aminoglycosides Fluriquinolones Glycopeptides
BL - can be dose of interval adjusted
Carb - as above
Amino - same dose, interval adjust, check levels
Fluor - same dose, interval adjust, check QT
Glycopeptides - same dose, interval adjust, check levels
Interval adjusting is most relevant for;
Concentration dependent abx which have toxicity with high levels
Examples - amino glycosides and Glycopeptides
Why do you dose adjust Abx
Relevant for time dependent abX that have toxicity associated with high concentration peaks
Eg fluroquinolones
Important to be above MIC for as long as possible - only need to load and then give small frequent doses to remain above MIC
Abx that rely on renal clearance
Beta lactams, cephalosporins and car spends Amino glycosides Fluconazole Aciclovir Vanc
Abx that do not need adjustment with renal failure
Linezolid Clindamycin Amphoteracin Azitgromyxib Ceftriaxome Voriconazole
General principles of abx dose adjusting in CRRT
Abx with time dependent killing - if rapidly cleared by CRRT need to give more frequently
Abx with concentration dependent killing - if cleared rapidly dose should be increased
If RRT is intermittent eg SLED should give at the end of each session
Drugs with large Vd, which do not rely on renal clearance
Eg - don’t need changes with RRT
Ceftriaxone Moxifloxacin Clindamycin Linezolid Voriconazole
Drugs that have large Vd and rely on renal clearance - need to have increased dosing interval as the filter can’t act the same way as the kidney with active pumps
Levofloxacin
Ciprofloxacin
Colostin
Amphiteracin
Drugs with small Vd that do rely on renal clearance - doe shouldn’t be adjusted with RRT as the filter can act as kidney in terms of glomerular filtration action
Beta lactams Carbapenems Amino glycosides Glycopeptides Fluconazole
MAY need to increase dose as filter may be more efficient esp fluconazole which must be increased at high filter rates
Time dependent Abx
Beta lactams Carbapenems Monobactams Linezolid Clindamycin Macrolides
Abx that kill bacteria most effectively when the bacteria are about to divide
Concentration dependent killing abx
Amino glycosides
Metronidazole
Daptomycin
Drugs that affect bacterial metabolism or protein synthesis; higher concentration means more enzyme molecules are inhibited
Time and concentration dependent killing
Fluroquinolones Azithromycin Tetracyclines Vanc Tigecycline
Drugs that inhibit DNA synthesis or other components of cellular division
Why are Abx not working
Wrong dose
Delayed dose
Inadequate source control
Inadequate blood levels
Inadequate penetration
Anti microbial neutralisation or antagonism
Superinfection or unsuspected secondary infection
Non bacterial infection
Non infectious source of illness
Eagle effect - paradoxical loss of effect
Factors that influence Abx choice
Disease factors - travel hx, occupation, ivdu, reliability of cultures
Host factors - age, allergies, pregnancy
Organism factors - source control, susectibility,
Drug factors - cost, toxicity, drug synergy
MIC definition
The lowest concentration of an antimicrobial that will inhibit visible growth of an organism after overnight incubation
Lower MIC = more effective
Drugs with post antibiotic effect
Those with concentration dependent kill characteristics; Amino glycosides Clindamycin Macro life's Tetracyclines Rifampicin Dalfopristin
Is when effects are seen long after concentration below MIC
Drugs with no post Abx effect
Beta lactams
Cephalosporins
Monobactams
These would benefit from continuous infusion
Polyenes
Antifungals - Amphiteracin and nystatin
They weaken cell wall
Amphiteracin
Active against fungi and yeast
Large Vd
No reliance on renal clearance
Toxicity - nephrotoxic, hypokalaemia, fever Ags chills, RTA, hypochromic normocytic anaemia
Azoles
Antifungals
Fluconazole, Voriconazole
Prevent synthesis of ergosterol
Early generations are only active against candida albicans and, most non albicans and are resistant
Fluconazole
Candida albicans Other candida resistant Active against cryptococcus No activity against aspergillus Penetrates into CSF Small Vd Relies on renal clearance, readily cleared by dialysis Toxicity - LFTS, alopecia, drug interactions (inhibits CYP 450)
Prophylaxis - use does not reduce mortality IV surgical pts
May reduce mortality if given in septic shock
Voriconazole
Covers all candida, cryptococcus, aspergillus
Highly protein bound
Vd massive
Not renally cleared, not dialysable
Inhibits CYP 450
Toxicity - long Qt, hallucinations, psychosis, drug interaction
Echinocandins
Anti fungal eg caspofungin
Inhibit cell wall synthesis by blocking synthesis of glycine 1,3 beta glucose synthase
Very active against candida, useless for cryptococcus, not very helpful for aspergillus
Highly protein bound
But dependent on renal excretion, not dialysable
Minimal toxicity
Toxicities of linezolid
Thrombocytopaenia Anaemia Neuropathy Lactic acidosis Serotonin syndrome
All due to mitochondrial toxin activity
Teicoplanin toxicity
Renal or liver dysfunction
Thrombocytopaenia
Anaemia
Tigecycline toxicities/se’s
N&V,
Teratogenic
Daptpmycin toxicity
Myopathy
Indicators of severity in CAP
Minor- RR >30 PF <250 confusion raised urea low WCC low plat low temp low BP
Major -
- invasive ventilation
- need for vasopressors
Slow reponders to treatment in pneumonia
aspergillus Q fever TB nocardia leptospirosis melioidosis
Risks for VRE
long admission renal impariment enteral tube feeding proximity to VRE patients elderly long term IV access inter hospital transfer low staff:patient ratio haematological malignancy multiple courses of Abx
Risks for C diff
Abx exposure - cipro ,clinda, beta lactams, cephalo immunosuppresant drugs, cytotoxic drugs age >65 PPI renal impairment long admission
treatment of VRE
linezolid
teicoplanin (if Van B)
daptomycin
tigecycline
consequences of VRE
systemic infection - determined by site of infection
transfer of resistance to staph aureus
qSOFA pros and cons
Easy
Has good predictive validity (AUROC 0.81)
BUT -
- validated retrospectively
- “new onset” vs old changes??
- not proven to be valid in a range of clinical settings
non-albicans candidaemia is associated with;
Repeated abdominal surgeries Exposure to broad-spectrum antibiotics Exposure to fluconazole Diabetes CVC insertion TPN use Malignancy Renal failure
Complications of candidaemia
Candida endopthalimitis/retinitis Candia endocarditis Hepatosplenic abscesses Pulmonary cavitating lesions CNS involvement (meningitis or abscesses) Candida arthritis
Lab confirmation of malaria
Thick (parasite load) and thin (parasite species) blood smears
Rapid diagnostic tests utilising malarial antigens (dependents on specific test)
firstline drugs for malaria
Cinchona alkaloids (quinine and quinidine) Artemisinin derivatives (artesunate, artemether).
Also -
tetracyclines (eg doxycycline), napthoquinones (eg. atovaquone) and lincosamides (eg. clindamycin).
Acute complications of malaria
Cerebral Involvement with or without convulsions
Respiratory Failure - acute respiratory distress syndrome (ARDS)
Circulatory collapse
GI -
• Renal failure, hemoglobinuria ("black water fever")
• Hepatic failure
• Splenic Rupture
- hepatosplenomegaly
Haematological
• Disseminated intravascular coagulation
• Severe anemia secondary to Haemaolysis
• Thrombocytopenia
Metabolic • Hypoglycemia • Severe Acidosis • Hyponatraemia -high fever and rhabdo due to rigors
Steps to take if approaching Ix of increase in infection rate (eg MRSA)
Investigate the validity of the reported colonisation rate
Investigate the demographics of the colonised patients
Investigate the origin of the patients (which ward are they coming from?)
Revisit the current infection control policy: is it time to rewrite it?
Get expert opinions from infectious diseases and infection control specialists
Form a multidisciplinary review panel (ICU specilists, ID physicians, NUMS and RNs)
Review the current literature on infection control
Rewrite infection control policy
Educate the staff regarding the new policy
Implement rigorous standards regarding hand washing and bed space cleaning
Monitor the effects of the implemented policies
differential causes of puprura fulminans
DIC from any cause
Sepsis due to the following organisms:
- S.pneumoniae - but mainly in asplenic patients for some reason
- S.aureus
- H.influenzae
- N.meningitides
Endocarditis of any bacterial aetiology
MAHA (microangiopathic haemolytic anaemia)
TTP (thrombotic thrombocytopenic purpura)
Varicella infection
Rickettsial infection
Plasmodium falciparum malaria
Vasopressor excess
Warfarin-induced skin necrosis
Congenital Protein C anticoagulant pathway defect
Post-infectious purpura fulminans (due to autoimmune destruction of proteins C or S)
Risk factors for CMV in the immunocompetent host
Critical illness in general seems to be a risk factor.
Risk factors for reactivation:
- Trauma
- Burns
- Severe critical illness (high APACHE score, over 27)
- Blood transfusion
- Mechanical ventilation
- Severe sepsis
- Prolonged ICU stay
- Pregnancy
diagnosis of CMV
Positive CMV antibodies (IgM) - sensitive for recent or acute infection
Qualitative PCR - very sensitive for the presence of CMV, but they do not distingusih between active and latent infection.
Quantitative PCR - ideal test, as it provides a quantitative assessment of viral load, and allows the monitoring of therapy.
complications of CMV
Colitis Hepatitis Encephalitis Guillain-Barre syndrome Pneumonitis (rare) Pericarditis and myocarditis Uveitis and retinitis
Complications of CMV in the Immunocompromised (transplant) host
Chronic allograft nephropathy (renal transplant)
Hepatic artery thrombosis (liver transplant)
Accelerated Hep C recurrence (liver transplant)
Bronchiolitis obliterans (lung transplant)
New onset NIDDM
Post-transplant lymphoproliferative disease
Management of CMV infection
Ganciclovir - initially
valganciclovir - when infection under control
Resistant strains - foscarnet and cidofovir
Virology of CMV
May be present in breast milk, saliva, feces, and urine.
Not readily spread by casual contact. Requires prolonged or intimate exposure.
Once infected, it is carried for life.
Reactivation occurs when T-cell immunity is impaired.
In organ transplant recipients, the transplanted organ is often the reservoir.
“Cytomegalovirus” is so called because… (interesting facts - because i dont have enough to learn)
the affected cells are two to four times the size of unaffected cells.
These cells typically have large “owl’s eye” inclusions
treatment options from MRSA aside from vanc
Tigecycline
Linezolid (particularly for MRSA pneumonia, where vancomycin penetrates poorly)
Quinupristin/dalfopristin
Daptomycin
Fosfomycin (usually to enhance the effects of other drugs)
Rifampicin/fusidic acid (particularly for deep bone and joint infections)
Telavancin, dalbavancin and oritavancin
Ceftobiprole and ceftaroline
Iclaprim
Trimethoprim/sulfamethoxazole
Moxifloxacin
Non infectious causes of fever
Vascular
- Cerebral infarction/hemorrhage
- Myocardial infarction
- Ischemic bowel
- Subarachnoid hemorrhage
- Fat emboli
- Deep venous thrombosis/PE
- Phlebitis/thrombophlebitis
Neoplastic
- Lymphoma-associated fever
- Renal cell carcinoma
- Tumour lysis syndrome
Drug-induced
- Alcohol/drug withdrawal
- Drug fever
Idiopathic inflammatory
- Postoperative fever (48 h postoperative)
- Acalculous cholecystitis
- Pancreatitis
- Aspiration pneumonitis
- ARDS
- Gout/pseudogout
- IV contrast reaction
- GI bleed
Autoimmune
- Posttransfusion fever
- Transplant rejection
- Vasculitis
- Haemolytic anaemia
Traumatic/environmental
- Haematoma degradation
- Decubitus ulcers
- Heat stroke
Endocrine
- Adrenal insufficiency
- Thyrotoxicosis
- Thyroiditis (Hashimoto)
- Ovulation/pregnancy
Biochemical markers of sepsis include:
CRP Procalcitonin LPS-binding protein sTREM-1 Presepsin (sCD14-st) HMGB-1
mechanisms that lead to vasodilation in sepsis
Nitric oxide synthase induction by cytokines and endotoxin
Direct vascular smooth muscle response to acidosis and hypoxia
Inflammatory mediators produced by activated leucocytes
Vasodilatory mediators (eg. histamine bradykinin and serotonin) produced by leukocytes and platelets
Relative vasopressin deficiency
Relative adrenal insufficiency, resulting in peripheral catecholamine insensitivity
Acidosis, resulting in peripheral catecholamine insensitivity
Opportunistic infections and treatment
CMV - valganciclovir
Aspergillus - voriconizole or amphoteracin
Pneumocystis - bactrim
Nocardia - suphonamides
risk factors for Varicella pneumonia:
Immunocompromised Pregnancy Chronic lung disease Adults (greater risk compared to children) Smoking Number of spots - over 100
Causes of seizures in meningitis
cerebritis
cerebral venous sinus thrombus
increased intracranial pressure
abscess
causes of functional asplenia
sickle cell disease
alcoholic liver disease
coeliac disease
Risk factors for pneumococcal bacteraemia
Extreme of age <2 or >65 Chronic lung disease Asplenia both functional and anatomic Immunosuppression Transplant patients CSF leaks Cochlear implants
Risk factors for acalculous cholecystitis
Trauma with massive transfusion Any recent surgery Burns Sepsis TPN Prolonged fasting Critical illness in general
Radiological and Ultrasonographic Features of
Acalculous Cholecystitis
Thickened gall bladder wall (over 3.5-4mm) Pericholecystic fluid Intramural gas Echogenic or hyperdense bile sludge Sloughed mucosa Gall bladder distension
Pathogens commonly responsible for acalculous cholecystitis
E.coli Klebsiella Proteus Enterococcus Bacteroides
treatment of prosthetic valve IE
vancomycin, gentamicin and rifampicin
stereotypical criteria for toxic shock syndrome
High fever (> 38.9°)
Hypotension and shock
Rash consistent with diffuse macular erythroderma
Desquamation, particularly of the palms and soles
There are also non-diagnostic associated features:
Rapid onset: ~ 2 days
Staphylococcus may grow in the blood (but blood cultures otherwise negative)
Multisystem organ involvement
Pathogenesis of toxic shock syndrome
Some staphylococci produce a characteristic protein (the Toxic Shock Syndrome Toxin, or TSST-1, 2 and 3).
TSST activates T-cells directly, acting as a “superantigen” -> Massive inflammatory cytokine release
Endothelial dysfunction and vasodilatory shock ensues, which is out of proportion to the severity of the initiating infection.
Risk factors for toxic shock syndrome
Being female Use of tampons Mastitis Sinusitis Osteomyelitis Burns Compromised immune system (eg. HIV)
Adjuncts to management that involve toxin/endotoxin
Clindamycin as an adjunct (prevents the synthesis of TSST) Intravenous immunoglobulin (to bind circulating TSST)
tests to do with meningitis if gram stain negative
Herpes Simplex PCR Mycobacterium Tuberculosis PCR Mycobacterial Stain and Cultures India Ink Stain, Cryptococcal Ag Fungal cultures Bacterial PCR
ways to decrease risk of CVC infection:
Intelligence use of CVCs (i.e. does the patient even need one?)
Subclavian lines.
Minimum number of lumens.
Use of dedicated lumens for lipid infusions.
Immunosuppressed patients or those with burns should have antibiotic-coated lines.
For insertion, use aseptic technique and maximal barrier precautions.
0.5% chlorhexidine in 70% alcohol is the preferred cleaning agent.
Handle ends of administration sets with gauze soaked in chlorhexidine).
Review the line daily.
Remove the line as soon as possible.
Change lines early - ideally, every 7 days.
Sterile, transparent semipermeable dressings
Change dressings regularly (every 7 days for standard dressings)
Alternative pathogens causing pseudomembranous colitis
Strongyloides stercoralis Staphylococcus aureus Clostridium perfringens Yersinia CMV Entamoeba Listeria
All the enterohaemorrhagic diarrhoea organisms:
- Salmonella
- Shigella
- Campylobacter
- E.coli
treatment for moderate - severe pneumonia
beta lactam and macolide (eg azithromycin 500mgod)
Continue for 7-10 days
NB - mild/mod infection; ceph and azithro, 5 days
Aetiology of nosocomial infection in ICU:
Pneumonia: VAP or HAP
Central line associated bacteraemia
UTI due to indwelling catheters
Sinusitis due to nasogastric tubes
Acalculous cholecystitis due to parenteral nutrition
Pressure area infections
Meningitis or ventriculitis due to EVD infection
C.difficile infections due to broad-spectrum antibiotic use
Surgical site infections
Causes of raised lactate in sepsis
endogenous catecholamine release and used of adrenaline
Circulatory faliure due to hypoxia and hypotension
Cytopathic hypoxia - widespread microvascular shunting and mitochondrial failure
inhibition of pyruvate dehydrogenase by endotoxin
Coexistent liver disease
