Infectious Diseases Flashcards
Abx inhibiting cell wall formation
penicillins, cephalosporins, carbopenems
glycopeptides
Cephalosporins MOA
beta lactam, bactericidal, disrupt synthesis of bacterial cell walls by inhibiting peptidoglycan cross-linking
Cephalosporin resistance
changes to penicillin-binding-proteins, which are types of transpeptidases (cross-link peptidoglycan chains to form rigid cell walls)
Vancomycin MOA
Binding to D-Ala-D-Ala moieties, preventing polymerisation of peptidoglycans
Vancomycin resistance
alteration to terminal amino acid residues of NAM/NAG-peptide subunits
Vancomycin SE
nephrotpxic, ototoxic, thrombophlebitis, red man syndrome (with rapid infusion. Flushing, erythema, pruritis affecting face, neck, upper torso, due to mast cell and basophil histamine release. Resolves within 20 mins of stopping/slowing infusion)
50S protein synthesis inhibitors
Macrolides, chloramphenicol, clindamycin, linezolid, streptogrammins
Chloramphenicol
Inhibits peptidyl transferase
SE: aplastic anaemia
Clindamycin
Inhibits translocation
SE: C Diff
Macrolides
Inhibits translocation
SE: nausea (esp erythromycin), P450 inhibitor, prolonged QTc
Linezolid
Oxazolidinone, bacteriostatic + bacteriocidal
Highly active vs: MRSA, VRE, GISA
SE: thrombocytopenia (reversible), avoid tyramine (like MAOi)
30S protein synthesis inhibitors
aminoglycosides
tetracyclines
aminoglycosides
Gentamicin
Causes misreading of mRNA
SE: ototoxicity, nephrotoxicity (ATN). Contraindication: Myasthenia. Monitoring: peak + trough levels
Tetracyclines
Blocks binding of aminoacyl-tRNA
Resistance: increased efflux by plasmid-encoded transport pumps, ribosomal protection
SE: teeth discolouration, photosensitivity, angioedema, black hairy tongue
Contraix: pregnant, breastfeeding women, children <12yrs
DNA synthesis inhibitors
quinolones
Quinolones
cipro/levofloxacin.
Inhibits topoisomerase II (DNA gyrase) and IV.
Resistance with mutations to DNA gyrase, efflux pumps as well.
SE: lowers seizure threshold, tendon damage (increased with steroids), cartilage damage, long QTc.
Contraindicated in pregnancy/breastfeeding and G6PD
Metronidazole
damages DNA
Folic acid formation inhibitors
trimethoprim, sulphonamides
Trimethoprim
MOA: inhibits dihydrofolate reductase (may interact with methotrexate) → inhibits DNA synthesis
SE: myelosuppression, transient creatinine rise (due to competitive inhibition of tubular creatinine secretion, with creatinine rise by 40, reversible), Type 4 RTA (blocks ENaC channel in distal nephron), teratogenic
Rifampicin MOA
inhibits RNA synthesis
Bacteriocidal vs bacteriostatic abx
Bacteriocidal Abx: penicillins, cephalosporins, aminoglycosides, nitrofurantoin, metronidazole, quinolones, rifampicin, isoniazid
Bacteriostatic abx: chloramphenicol, macrolides, tetracyclines, sulphonamides, trimethoprim
Azoles
MOA: inhibits 14alpha-demethylase → reduces ergosterol production from lanosterol → reduces plasma membrane structural integrity/stability
SE: P450 inhibition, hepatotoxic
Terbinafine
MOA: inhibits squalene epoxidase → ultimately, reduced ergosterol production → reduces plasma membrane structural integrity/stability
SE: pancytopenia, agranulocytosis, hepatotoxic
Used orally to treat fungal nail infections
Echinocandins
(Gaspofungin/any -fungins)
MOA: beta-glucan synthase inhibition → prevents transport of beta glucans to cell wall to be used for its formation
SE: flushing
Amphotericin B
MOA: binds to ergosterol forming transmembrane channel makining little tears (AmphoTEARicin)→ leads to monovalent ion (K, Na, H, Cl) leakage + cell death
SE: nephrotoxicity, flu-like sx, hypoK, hypoMg, hepatotoxic, phlebitis
Used for systemic fungal infections
Nystatin
MOA: binds to ergosterol forming transmembrane channel makining little holes → leads to monovalent ion (K, Na, H, Cl) leakage + cell death
Very toxic, can only be used topically (e.g. for oral thrush)
Griseofulvin
MOA: interacts with microtubules, disrupts mitotic spindle
SE: CYP450 inducer, teratogenic
Flucytosine
MOA: converted by cytosine deaminase to 5-fluorouracil, inhibits thymidylate synthase → attacks DNA → disrupts fungal protein synthesis
SE: vomiting
DNA polymerase inhibitor antivirals
aciclovir, ganciclovir, foscarnet
Aciclovir
MOA: guanosine analogue, phosphorylated by thymidine kinase, inhibits viral DNA polymerase
For HSV, VZV
SE: crystalline nephropathy
Ganciclovir
MOA: guanosine analogue, phosphorylated by thymidine kinase, inhibits DNA polymerase
For CMV
SE: myelosuppression/agranulocytosis
Foscarnet
MOA: pyrophosphate analogue, inhibits DNA polymerase
For CMV, HSV (2nd line)
SE: nephrotoxicity, hypoCa, hypoMg, seizures
antiviral mRNA group
IFN alpha, ribavirin
IFN alpha
MOA: inhibits mRNA synthesis
For HBV, HV, hairy cell leukaemia
SE: flu like sx, myelosuppression
Ribavirin
MOA: guanosine analogue, inhibits IMP dehydrogenase, interferes with mRAN capping
For chronic HCV, RSV
SE: haemolytic anaemia
M-group antivirals
amantadine, oseltamivir
Amantadine
MOA: inhibits M2 protein and uncoating of virus, releases dopamine from nerve endings
For influenza, PD
SE: confusion, ataxia, slurred speech
Oseltamivir
MOA: neuraminidase inhibitor
For influenza
Cidofovir
MOA: acyclic nucleoside phosphonate, independent of phosphorylation by viral enzymes
For CMV retinitis in HIV
SE: nephrotoxicity
E coli gastroenteritis
Cause: E Coli (facultative, anaerobic, lactose-fermenting, G-ve rod). ETEC produces toxins stimulating intestinal lining → excessive fluid. EHEC can cause bloody diarrhoea
Incubation period 12-48hrs
Sx: onset within 1st wk of travel. Commonest cause of traveller’s diarrhoea (at least 3 episodes within 24hrs). Watery diarrhoea, abdo cramps, nausea
Giardiasis
Transmission: Giardia lamblia, faeco-oral.
RF: travel, swimming/drinking from river/lake, male-male sexual contact
Incubation period >7 days
Sx: prolonged non-bloody diarrhoea, steatorrhoea, bloating, abdo pain, lethargy, flatulence, weight loss, malabsorption, lactose intolerance
Ix: stool MCS for trophozoites, cysts (sensitivity 65%), stool antigen detection assay (greater sensitivity, faster), PCR assays.
Rx: metronidazole
Cholera
Cause: vibrio cholerae (G -ve)
Sx: profuse, watery diarrhoea with severe dehydration, weight loss, hypoglycaemia
Rx: oral rehydration therapy. Abx: doxy, ciprofloxacin
Shigella
Cause: S sonnei (mild), S flexneri, dysenteriae (severe)
Incubation period: 48-72hrs
Sx: bloody diarrhoea, vomiting, abdo pain
Rx: self limiting, but ciprofloxacin if severe, bloody or immunocompromised
Salmonella
Cause: aerobic, G-ve rods of Salmonella group, are not gut commenals. Salmonella typhi and paratyphi (types A, B, C) cause enteric fevers. Faeco-oral transmission
Incubation period 12-48hrs
Sx: Enteric fever (headache, fever, arthralgia), relative bradycardia (Faget sign), abdo pain, distension, constipation (more common than diarrhoea), rose spots on trunk 40% (more common in paratyphoid)
Compl: osteomyelitis (esp in Sickle cell disease), GI bleed/perforation, meningitis, cholecystitis, chronic carriage (1%, more likely with adult F)
Ix: Large volume blood culture
Rx: Typhoid - ceftriaxone. Non-typhoid - ciprofloxacin
S aureus gastroenteritis
Incubation period: 1-6hrs
Sx: severe vomiting
Campylobacter
Cause: Campylobacter jejuni (G-ve bacillus), faeco-oral, undercooked poultry, unpasteurised milk
incubation period 1-6 days
Sx: prodrome (headache, malaise), bloody diarrhoea, abdo pain, mimics appendicitis
Rx: self-limiting. Clarithromycin if severe (high fever, bloody diarrhoea, >8 stools/day, >1wk) or immunocompromised. Alt: ciprofloxacin
Compl: GBS, reactive arthritis, septicaemia, endocarditis, arthritis
Bacillus cereus
Cause: undercooked rice
Incubation period 1-6hrs
Sx: Vomiting within 6hrs or diarrhoeal after 6hrs
Amoebiasis
Cause: entamoeba histolytica, faeco-oral. 10% chronically infected
Incubation period >7 days
Sx: can be asymptomatic, mild diarrhoea or gradual onset bloody diarrhoea, abdo pain, lasting several wks, can form liver/colonic abscesses
Amoebic dysentery:
Sx: profuse, bloody diarrhoea, long incubation period
Ix: Stool microscopy - trophozoites (examine within 15 mins or keep warm - ‘hot stool’)
Amoebic liver abscess:
Sx: fever, RUQ pain, systemic, hepatomegaly, ‘anchovy sauce’ contents of liver
Ix: ultrasound, serology >95%
Rx: oral metronidazole + luminal agent (e.g. diloxanide furoate
S aureus pneumonia
post-influenza, cavitation lung lesions (esp with strains producing Panton-Valentine Leukocidin cytotoxin → necrotic, haemorrhagic pneumonia)
S pneumoniae assx
herpes labialis
Mycoplasma pneumoniae
Sx: younger pts, epidemic every 4 yrs, prolonged, gradual onset, flu-like sx then dry cough
Compl: cold agglutinins (IgM), haemolytic anaemia, thrombocytopenia, erythema multiforme, erythema nodosum, meningoencephalitis, GBS, bullous myringitis (painful vesicles on tympanic membrane), pericarditis/myocarditis, hepatitis, pancreatitis, acute glomerulonephritis
Ix: CXR b/l consolidation, dx by serology. +ve cold agglutination test, blood smear shows RBC agglutination
Rx: doxycycline/macrolide (lacks peptidoglycan cell wall)
Legionella CAP
Cause: Legionella pneumophilia, intracellular bacterium, water tanks (dodgy air-conditioning, foreign travel)
Sx: flu-like 95%, dry cough, relative bradycardia, confusion
Ix: dx by urinary antigens, hypoNa, deranged LFTs, lymphopenia, CXR (mid-lower zone consolidation, pleural effusions 30%)
Rx: macrolide
Pstitacosis
Cause: Chlamydia psittaci. An obligate intracellular bacterium. Via birds/bird secretions
Sx: flu-like + resp (dry cough). Sometimes hepatosplenomegaly
Ix: CXR consolidation, serology
Rx: 1. Doxy. 2. macrolides
Klebsiella pneumonia
Cause: G -ve rod, part of normal gut flora. Common in alcoholics (due to ETOH-induced dysbiosis → intestinal immune response alterations). May occur following aspiration
Sx: ‘red-currant jelly’ sputum, often affects upper lobes. Cavitation lesions
Prognosis: commonly causes lung abscess formation + empyema, mortality 30-50%
HAP Rx
<5 days of admission: co-amox/cefuroxime
>5 days post-admission: tazocin/broad-spectrum ceph/quinolone
CURB65
confusion (AMTS<8), Urea >7, RR>30, BP <90/60, Age>65. Admit if 2 or more.
LUTI causes
E Coli commonest (G -ve)
Staphylococcus saprophyticus 2nd most common in sexually active young women (G +ve, clusters, coagulase -ve)
Rx for LUTI
Non-pregnant: if symptomatic, trimethoprim/nitrofurantoin 3 days
Pregnant: 1. Nitrofurantoin 2. amoxicillin/cefalexin. Avoid trimethoprim in 1st trimester. Treat for both asymptomatic + symptomatic
Men: 7 days trimethoprim/nitrofurantoin
Catheterised: treat only if symptomatic
Pyelonephritis Rx
ceph/quinolones 10-14 days
Meningitis causes
0-3months: Group B strep (esp neonates), E Coli, Listeria monocytogenes
3months - 6yrs: (NHS) N meningitidis, H Influenzae, S pneumoniae
6-60yrs: (-H to NHS) N meningitidis, S pneumoniae
> 60yrs: (replace H with L in NHS) N meningitidis, S pneumoniae, Listeria monocytogenes
Immunosuppressed: Listeria monocytogenes
Viral: non-polio enteroviruses (Coxsackie, echovirus), mumps, HSV, CMV, HZV, HIV, measles
CSF in meningitis types
Bacterial: cloudy appearance, low glucose (<50% of plasma), high protein, WBC polymorphs
Viral: clear/cloudy, glucose 60-80% of plasma (low glucose in mumps, Herpes encephalitis), WBC lymphocytes
TB: slightly cloudy, fibrin web, low glucose (<50% of plasma), high protein, WBC lymphocytes. Zielh-Neelson stain only 20% sensitive, PCR more sensitive (75%)
Fungal: cloudy, low glucose, high protein, WBC lymphocytes
Abx in meningitis
<3 months: cefotaxime + amoxicillin
3 months - 50 yrs: cefotaxime/ceftriaxone
> 50 yrs: cefotaxime/ceftriaxone + amoxicillin
Meningococcal: benzylpenicillin or cefotaxime/ceftriaxone
Pneumococcal: cefotaxime/ceftriaxone
Haemophilus influenzae: cefotaxime/ceftriaxone
Listeria: amoxicillin + gentamicin
Pen/ceph allergic: chloramphenicol
When to avoid dex in meningitis
Avoid in septic shock, meningococcal septicaemia, immunocompromise, post-surgical meningitis
Contacts Rx in meningitis
for those exposed to meningococcus (risk highest 1st 7 days, persists for 4 wks) oral ciprofloxacin/rifampicin (cipro just needs one dose), meningococcal vaccination when serotypes available, including boosters, no prophylaxis for pneumococcal
Meningitis compl
sensorineural hearing loss (most common), seizures, focal neuro def, infective (sepsis, abscess), pressure (herniation, hydrocephalus), Waterhouse-Friderichsen syndrome (from meningococcal meningitis → adrenal haemorrhage → adrenal insufficiency
Cellulitis causes
S pyogenes, S aureus (less common)
Eron classification
I: no signs of systemic toxicity, no uncontrolled comorbidities
II: systemically unwell/ well + comorbidity (e.g. PAD, venous insufficiency, obese) that may complicate/delay resolution
III: significant systemic upset (confusion, tachycardia, tachypnoea, hypotension) or unstable comorbiditie
IV: sepsis with life-threatening infection such as nec fasc
cellulitis rx
Oral fluclox if Eron I. Alt: clarithromycin, erythromycin, doxycycline. 2nd line: clindamycin
IV Abx if Eron II
admit if Eron III/IV, severe/rapidly deteriorating cellulitis, very young/frail, immunocompromised, significant lymphoedema, facial/periorbital cellulitis. Choice of abx: co-amox, clindamycin, cefuroxime, ceftriaxone
Necrotising fasciitis causes
Type 1: mixed anaerobes, aerobes, often post-surgical, diabetics (most common)
Type 2: S pyogenes
Nec fasc RF
skin factors (trauma, burns, soft tissue inf), DM, SGLT-2 inh use, IVDU, immunosuppression
