mechanisms of abx resistance
may be intrinsic
evoked or evolved
- inactivation - enzyme production e.g. beta lactamase
- target site modification - structural changes to bacterial components e.g. ribosomes
- decreased cell wall permeability - structural changes
- active expulsion - efflux pumps
common resistant organisms
MRSA: sensitive to vanc / teic
C.diff
VRE: linezolid, tigeycline
ESBL (e.coli / klebsiella): carbapenem
Carbapenemase producing enterobacteracae CPE
Pseudomonas: piptaz, quinolones, carbapenems
antimicrobial stewardship
infection control, judicious abx management
optimise drug choice, timing, dose and duration to eradicate infection and reduce negative effects of antimicrobials (nosocomial infection, resistant organisms)
strategies in antimicrobial stewardship
PCT for de-escalation
bactericidal activity of antibiotics
Minimum inhibitory concentration MIC - concentration of antimicrobial required to completely inhibit visible growth
time-dependent killing - bactericidal when concentration above MIC consistently
concentration dependent killing - bactericidal when peak concentration above a certain level
AUC / MIC - concentration and time dependent killing effects
SDD
selective decontamination digestive tract
SDD reduce overall mortality by 6%
Pyrexia in critical care
Systematic consideration of sources
A - dental abscesses, tonsilitis, sinusitis
B - Pneumonia, tracheitis, empyema
C - IE
D - meningitis, encephalitis, cerebral abscess
E - cellulitis, nec fas, septic arthritis, ifnected pressure sore
F - UTI, pyelonephritis
G - cholecytisits, peritonitis, diverticulitis, appendicitis
GU - PID, epidymo-orchitis, prostatitis
considerations invesitgating PUO
considerations of managing bacterial infection
stopping abx
individualised
clinical improvement - e.g. improved gas exchange, resolving pyrxexia
prolonged courses indicated in some situations - IE, osteomyeletis
biomakers
Common viruses in critical care
orthomyxoviridae - infuenza ABC
Coronaviridae - SARS, MERS, covid-19
Herpesviridae - HSV, VZV, CMV, EBV
paramyxoviridae - RSV, measles, mumps
flaviviridae - dengue
filoviridae - ebola
virus classification
DNA or RNA surrounded by protein capsid. capsid helical, icosahedral or complex. some have outer envelope or are naked
RNA
- icosahedral naked - picornavirus. enveloped - flavivirus
- helical enveloped - coronavirus, orthomyxovirus
- complex -retrovirus
DNA
- icosahedral naked - parvovirus
- icosahedral enveleoped - herpes
challenges of fungal infections in critical care
types of fungal infections
moulds : aspergillus
yeasts : candida, cryptococcosis
dimorphic : histoplasma
primary: immunocompetent patients. abundant spores and some innate virulence
secondary : opportunistic, less innate virulence but cause disease in immune impaired
risk factors for fungal infection
invasive candidiasis
commonest fungal infection in ICU
usually superficial colonisation but candidaemia has high mortality
haematagenous spread - heart, liver, brain, eyes
echo / ophthalmology review
positive blood cultures need detailed assessment
fluconazole / anadilafungin treatment
aspergillus
other fungal infections
PCP
- progressive dyspnoea, dry cough, exertion desaturation, air leaks
crpytococcus
- pulmonary cryptococcosis - infiltrative pneumonia
- meningoencephalitis - slow progressive
- relatively immune modulation - inflammation / immune reconstitution on treatment
mucormycosis
- disseminated infection, angio invasion, necrosis
fungal disease investigations
anti fungal classes
polyenes - amphotericin b - cell wall damage . cryptococcosis
azoles - voriconazole (aspergillosis), fluconazole (candida)- inhibit cell wall synthesis.
echinocadins - inhibit b glucan synthesis - caspo / anadulofungin
flucytosine - incoproated in rna
anti fungal side effects
fluconazole / voriconazole - liver, qtc, cytochrome p450
anidulafungin - liver
amphotericin - renal, eleectrolyte
anti fungal prophylaxis
nosocomial infection definition
common, preventable, increase mortality and morbidity