Infectious Diseases Flashcards
Mechanisms of resistance (3)
- Antibiotic - beta-lactamases, pneumococcus & macrolides, enzymatic modification of ahminoglycosides
- Alteration of target - pneumococcus & penicillin, staph. aureus and methicillin-like abx
- Decreased uptake - pseudomonas using porins for carbapenems, efflux pneumococcus & macrolides; pseudomonas & multiple agents
MIC definitions for MRSA, VISA and VRSA + mechanism
Vancomycin MIC
MRSA <2
VISA 4-8 = thicker cell wall - many more targets for vancomycin to bind prior to inactivating glycosyltransferase
VRSA >16
VRE - which, how, risk, treatment
Enterococcus faecium more common than faecalis
Van A, B, and C genes - changes D-ala-D-ala to alter binding, eliminates it, dipeptidase to cleave it
Van A will be also resistant to teicoplanin
Risk increased with anti-anaerobic abx
Treat with ticoplanin, linezolid, daptomycin, tigecycline
Penicillin resistance definition in normal vs meningitis
Sensitive <2
Intermediate 4
Resistant >8
Meningitis
Sensitive <0.06
Resistant >0.12
26M brought into ED with severe dyspnoea, hypoxia and fevers. Rapidly requires intubation and transfer to ICU for mechanical ventilation and vasopressors. See CXR. Needle marks in left cubital fossa. Soft ESM. Appropriate antibiotic therapy?
A. Benzylpenicillin and doxycycline
B. Ceftriaxone and azithromycin
C. Benzylpenicillin, flucloxacillin and gentamicin
D. Vancomycin, ceftriaxone and azithromcyin
E. Linezolid and meropenem
D. Vancomycin, ceftriaxone and azithromcyin
IVDU - more likely to have MRSA
Beta-lactamase enzymes - Ambler classes
A - Penicillinases (TEM, SHV, CTX-M)
B - Metalloenzymes (NDM, VIM, IMP)
C - Cephalosporinases (AmpC)
D - Oxacillinases (OXA)
Organism with Class C - inducible beta-lactamase
ESCAPPM - AmpC-type - chromosome mediated
Enterobacter (E. cloacae & K. aerogenes)
Serratia marcescens
Citrobacter freundii
Acinetobacter
Providencia spp.
Proteus (Indole-positive i.e., P. vulgaris)
Morganella morganii
Class A - EXTENDED-SPECTRUM BETA-LACTAMASES (ESBL)
- how they arise
- spread
- which bugs
- treatment
Arise by:
* Mutations in old β-lactamase genes (e.g., TEM, SHV)
* Plasmid-mediated transfer
Spread by:
* Person to person
* Antibiotic pressure
Klebsiella, E. coli, Salmonella, Proteus, Enterobacter, Citrobacter, Serratia, Pseudomonas
* In vitro inhibition by beta-lactamase inhibitors
* Can be hard to detect in the lab
Treat with:
* Carbapenems, colistin, amikacin, cipro (fosfomycin or nitrofurantoin for cystitis)
CLASS B – METALLO-BETA-LACTAMASES
- Zn-dependent
- Pseudomonas & Acinetobacter
- Plasmid mediated usually
- Hydrolyse all beta lactams (except aztreonam)
- Includes carbapenems
- Susceptible to ion chelators like EDTA
- New Delhi version = NDM
72F admitted with sepsis from presumed urinary source. BC positive with Klebs. pneumoniae and is found to be ESBL; susceptible to mero & colistin. MIC for piperacillin/tazobactam is 2 mg/l
Which of the following is true?
A. Colistin should be the first-choice therapy
B. Standard q8 hourly dosing of pip/taz is acceptable
C. Use a higher dose of q6 hourly pip/taz
D. Even with the lowish MIC, pip/taz is inferior to mero
E. Mero is too much of a hassle because you’ll need to get an approval number from the AMS team
D. Even with the lowish MIC, pip/taz is inferior to mero
In vitro activity often looks better
MERINO Trial demonstrated mortality benefit of meropenem
New drugs against gram positives
- Linezolid
- inhibits protein synthesis, no advantage over vanc
- GI, cytopenia, neuropathy
- avoid SSRI, tramadol, pethidine - Daptomycin
- binds cell membrane inhibiting DNA, RNA, protein synthesis
- not for pneumonia - surfactant inhibits it
- effective against VRE - Tigecycline
- protein synthesis inhibitor
- low MIC for MRSA, MSSA, VISA, VRE - Ceftaroline (& ceftobiprole)
- new cephalosporin that is active for MRSA, NOT VRE
- works for MRS, VISA, NOT VRE
Drugs for gram negatives
- Colistin
- binds LPS & phospholipids > leakage + death
- renal + neurotoxicity
- against: Pseudomonas, Acinetobacter, E. coli, some Enterobacter spp., Klebsiella, Salmonella, Stenotrophomonas - Fosfomycin
- inhibits MurA required for cell wall synthesis
- for resistant UTIs - New combinations = ceftazidime+avibactam or ceftolozane+tazobactam
- for MDR Gram negatives including pseudomonas & ESBL - Cefiderocol
- binds iron
- for multi-resistant GNBs
- expensive
- SE: GI, LFTs, rash, injection site
Vancomycin + Pip/Taz = what issue
- Increased rates of AKI, especially >48hrs
- no association with vanc levels > due to pip/taz
- extrapolate to other penicillins
Antibiotic prophylaxis (4 categories)
- Cesarean, head&neck, thoracic, ortho - cefazolin
- Major ENT, GI, infrarenal vascular - Cefazolin + metronidazole
- Amputation - benzpen
- ERCP - gent
35F in ICU postMVA with multiple fractures and splenic laceration=> splenectomy. Remains intubated on D8, on cefazolin. Deteriorates with low BP, high HR, increasing respiratory requirements and high WCC. Started on empiric pip/taz and vanc for sepsis ?VAP. BC –ve and tracheal aspirate has mixed bugs incl. GNBs. 3 days later, still unwell, noted to have rise in creatinine from 110 to 236 μmol/L.
Which is true regarding the patient?
A.This is likely to represent augmented renal clearance in a young, previously
healthy patient
B. If no MRSA cultured, vanc could be safely ceased
C. They should be urgently vaccinated for the encapsulated organisms (pneumococcus, HiB, meningococcus)
D. Continue the vanc/pip/taz as it is more important to control the sepsis than worry about the kidneys
E.It is not appropriate to swap the pip/taz to cefepime as there is too much resistance to cefepime in ICU patients
B - true
A/D - incorrect, as this is AKI induced by vanco/pip/taz combo
C - when well or prior to splenectomy
TB - path, risk, therapy
Path - infects macrophages, elicits granuloma formation, resistance to ROS, inhibits lysosome fusion, and phagosome acidification
Resistance via point mutation
Risk - HIV, >15mg pred for >1 month, other immunosuppression
Therapy - 2HREZ + 4HR
- longer if big cavity or smear positive at 2 months, CNS, resistant, skeletal, or disseminated
- similar in pregnancy
TB paradoxical reaction
- Clinical or radiological deterioration of pre-existing lesions or else the appearance of new lesions whilst on therapy
- Median 2-3 months
- Presents with fever, nodes, resp. failure, neuro
deterioration, sinus formation - Treatment - continue current, corticosteroids +/- pus aspiration or excision, last line is anti TNF
MAC lung infections - 2 subtypes
Nodular bronchiectasis (NB)
* Little old white ladies, mainly in RML, lingular segment
* Multiple genotypes, often smear –ve & only grow in broth
Fibronodular Cavitatory (FNC)
* Middle-aged, male smokers/drinkers
* Single genotype, heavy growth
Treatment =
- Azithromycin + rifampicin + ethambul
- 3x weekly for NB or daily for FNC for 2 months
When trying to work out whether a patient with 6 weeks of cough with LOW and haemoptysis has TB, the Quantiferon Gold Assay can help in which of the following ways?
A. The degree of positivity can help differentiate latent from active TB
B. A negative result means that TB is so unlikely that other diagnoses are much more important to pursue
C. With successful therapy, the test will go from positive to negative some months later
D. A positive test can be caused by prior BCG vaccination
E. Neither a positive nor a negative result will help with ruling in or out the diagnosis of active TB so there is no point doing the test
E
Quantiferon Gold is a screening assay. It can be negative in acute infection and once it’s positive it just indicates exposure, cannot tell if it is active or latent.
Oseltamivir - moa and effect
Neuraminidase inhibitor - stops release of virions
Reduces symptoms and spread
Remember in H&N in Flu with haemagglutinin responsible for entry
Pertussis - phases and treatment
Phases (generally no fever)
- sometimes catarrhal (“cold”)
- Paroxysmal
- Convalescent
PCR
Azithromycin
89F from HLC NH sent to ED after starting to cough while eating soup for dinner. SOB, moist sounding cough, CXR shows RML infiltrate.
Which of the following is true?
A. Oral anaerobes are only susceptible to metronidazole & not penicillins or cephalosporins
B. Culture the soup ASAP
C. Should use pip/taz to cover all Gram negs and anaerobes
D. Aspiration pneumonia requires specific anti-anaerobic therapy
E. Aspiration pneumonitis just requires respiratory support until it resolves without antibiotics
E - if systemically unwell or not improving by day 2/3 then treat as CAP
When to consider PO switch in bone & joint infections?
1 week per OVIVA Study
Old 3-6 week rule if critical such as axial skeleton, or clinical decision
Klebsiella pneumonia K1
Emerging in Asia (Taiwan)
Associated with: liver abscesses, endopthalmitis
Diabetics
Generally susceptible to ceftriaxone