bugs & drugs!
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8/8/2019 Bugs & Drugs!
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Bugs & Drugs!
Catrina Huang
MED V 2009
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Fever
Duration
Sweats- PM, cold + hot
Rigors- uncontrollable,
µhold a cup of hot h2ow/out spilling it?¶
Joint/ myalgia- bone pain(mets)
Meningitis- neck stiffness,
photophobia Other inf ections-
r espiratory, urination,bowel
Travel- 4W, H,vaccination
Sexual Hx- num of partner (M/ F),intercourse? Protection?STI? Rx? Compeleted?
Occupation
Animal contact
Foods (change) IVDU- past, curr ent
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µMust know¶ bugs
Gram +ve
± Cocci
±Bacilli
Gram ±ve
± Cocci
± Bacilli
Others
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Type of Organism Genus
Readily Gram-stained
Gram-positive cocci
Staphylococcus, Streptococcus,
Enterococcus
Gram-negative cocci Neisseria
Gram-positive rodsCorynebacterium, Listeria, Bacillus,C lostridium , Actinomyces, Nocardia
Gram-negative rods
*Enteric tract organisms
Pathogenic inside and outside tract E scherichia, Salmonella
Pathogenic primarily inside tract Shigella, Vibrio, Campylobacter, Helicobacter
Pathogenic outside tractKlebsiella-E nterobacter-Serratia group, Pseudomonas, Proteus-Providencia-Morganella group, Bacteroides
*Respiratory tract organisms Haemophilus, Legionella, Bordetella
*Organisms from animal sources Brucella, Francisella, Pasteurella, Yersinia
Not readily Gram-stained
Not obligate intracellular parasitesMycobacterium, Mycoplasma, Treponema,Leptospira
Obligate intracellular parasites Chlamydia, Rickettsia
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Gram +ve cocci
Staphylococci ± Staph aureus (& MRSA)
± Staph epidermidis
± (Staph saprophyticus)
Streptococci ± Strep pyogenes (group A str ep)
± Strep agalactiae (group B str ep)
± Strep pneumoniae (pneumococcus)
± Enterococcus faecalis
± Viridans Group str eptococci
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Gram +ve rods
Bacillus spp. ± B. anthracis
± B. cereus
Clostridium spp. ± C . tetani
± C . botulinum
± C . perfringens
± C . difficile
Corynebacterium diphtheriae
Listeria monocytogenes
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Gram +ve rods
Bacillus spp. ± B. anthracis: anthrax
± B. cereus: f ood poisoning ± beware the reheated (f ried)rice!
Clostridium spp. ± C . tetani: tetanus
± C . botulinum: botulism
± C . perfringens: gas gangrene (necrotising f asciits + myonecrosis), f oodpoisoning
± C . difficile: pseudomembranous colitis ± Abx-induced diarrhoea (mostcommon nosocomial cause of diarrhoea)
Corynebacterium diphtheriae: diphtheria
Listeria monocytogenes ± Foetus/newborn infection: meningitis, sepsis
± P regnant women, immunocompromised infection: meningitis, sepsis
± Unpasteurised milk products (sof t cheeses, sof t-serve ice cream, delimeats), undercooked meat, raw vegetables, contact with f arm animals,domestic animals, contaminated f aeces
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Gram ±ve cocci (diplococci)
Neisseria meningitidis (meningococcus)
Neisseria gonorrhoeae (gonococcus)
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Gram ±ve cocci
Neisseria meningitidis (meningococcus) ± Meningitis
± Meningococcaemia
Neisseria gonorrhoeae (gonococcus) ± Local: gonorrhoea, e.g . ur ethritis, cer vicitis
± Ascending: PID
± Disseminated: disseminated gonococcal inf ection
± Neonatal: gonococcal conjunctivitis (ophthalmianeonatorum)
± Wher e partner from? (diff er ent territories diff er ent Abx r esistance)
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Gram ±ve rods
Enteric tract
Respiratory tract
Animal sources (zoonotic organisms)
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G ±ve rods: Enteric
Bugs INSIDE & OUTSIDE the enteric tract
Escherichia coli Salmonella spp.
Bugs INSIDE the enteric tract
Shigella spp. Vibrio spp.
Campylobacter jejuni
Helicobacter pylori
Bugs OUTSIDE the enteric tract
K lebsiella-Enterobacter-Serratia group
P roteus-Morganella-P rovidencia group P seudomonas aeruginosa
± Burkholderia cepacia
± Stenotrophomonas maltophilia
Bacteriodes fragilis [main anaerobe in gut] ± P revotella melaninogenica
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G ±ve rods: Enteric
Bugs INSIDE & OUTSIDE the enteric tract
Escherichia coli: UTI, G ±ve septicaemia, traveller¶s diarrhoea, neonatal meningitis Salmonella spp.: typhoid (enteric f evers), enterocolitis, septicaemia
Bugs INSIDE the enteric tract
Shigella spp.: dysentery (i.e. bloody diarrhoea)
Vibrio spp.: Vibrio cholerae: cholera
Campylobacter jejuni: enterocolitis (major cause)
Helicobacter pylori: gastritis, peptic ulcer, RF f or gastric CA, linked to MALT (mucosal-associated lymphoid tissue)
Bugs OUTSIDE the enteric tract
K lebsiella-Enterobacter-Serratiagroup: hospital acquired pneumonia, UTI, septicaemia(invasive catheterisation, resp intubation, urinary tract manipulations)
P roteus-Morganella-P rovidencia group: UTI (hospital + community acquired)
P seudomonas aeruginosa: I.E. in IVDU, UTI, pneumonia (CF pt), inf ected burns, septicaemia.OPPORTUNISTIC NOSOCOMIAL INFECTION!
± Burkholderia cepacia
± Stenotrophomonas maltophilia
Bacteriodes fragilis [main anaerobe in gut]: sepsis, peritonitis, abdominal abscess
± P revotella melaninogenica
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G ±ve rods: Respiratory
Haemophilus influenzae
Bordetella pertussis
Legionella pneumophilia
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G ±ve rods: Respiratory
Haemophilus influenzae: ± Leading cause of meningitis in kids until Hib vaccine
± Children: URTI (otitis media, sinusitis, epiglottitis), sepsis
± Adults: pneumonia (esp. chronic obstructive lung dz pt)
Bordetella pertussis: whooping cough (pertussis)
Legionella pneumophilia: pneumonia (hospital +
community acquired; immunocompromised) ± Assoc. environmental water sources ± air con, water cooling
towers (taps, sinks, showers)
± Typical pt: old man, smoker, ETOH; AIDS pt, cancer pt,transplant pt, corticosteroid Rx
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G ±ve rods: Animal sources
P asteurella multocida
± Animal bites! Causes inf ection (cellulitis) of
bite wound
Brucella spp.
Francisella tularensis
Yersinia pestis
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Others
Mycobacteria ± Mycobacterium tuberculosis
± Atypical mycobacteria
± Mycobacterium leprae
Mycoplasmas
± Mycoplasma pneumoniae Spirochetes
± Treponema pallidum (syphillis)
Chlamydiae
± Chlamydia trachomatis
± Chlamydia pneumoniae
± Chlamydia psittaci
Rickettsiae
± Rickettsia rickettsii
± Rickettsia prowazekii
± Coxiella burnetti
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Staphylococcus aureus
Human nose! Skin Coagulase-positive staph (the only
one)
Abscesses (pointing lesions)
Pyogenic inf ections, i.e. pus-producing (endocarditis, septic
arthritis, osteomyelitis) Food poisoning
Scalded skin syndrome
Toxic shock syndrome
Hospital acquired pneumonia
Septicaemia
Surgical wound inf ections
Skin inf ections ± Folliculitis
± Cellulitis (localized, suppurative,µpointing¶ lesion, abscess)
± Impetigo (kids- worry 2daryinf ection?)
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Staphylococcus epidermidis
N. flora on skin + mucous membranes
Coagulase-negative staph
Prostheses/instrumentation inf ections ± Endocarditis on prosthetic heart valves
± Prosthetic hip inf ection
±Intravascular catheter in
f ection
± CSF shunt inf ection
Neonatal sepsis
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Streptococcus pyogenes (Group A str ep)
Suppurative (pus-producing disease) ± Pharyngitis (µstr ep throat¶)
± Skin + soft tissue inf ections (diffuse lesions) Cellulitis (acute illness, mor e diffuse, angry, r ed, hot)
Necrotising fasciitis (str eptococcal gangr ene) Impetigo
± Endometritis
Non-suppurative diseases (immunologic
diseases) ± Rheumatic f ever (pharyngitis) pharyngitisRF
± Acute glomerulonephritis (cellulitis) cellulitis GN
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Streptococcus agalactiae (Group B str ep)
Neonatal meningitis, sepsis
Adults: ± Pneumonia
±Endocarditis ± Arthritis
± Osteomyelitis
Diabetes = BIG risk factor for GBS inf ections
GBS colonisation in pr egnancy neonatal
inf ection (4th year) ± RF: GBS +ve mother, prolonged ruptur e of
membranes, pr ematur e labour, no maternal a/b
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Streptococcus pneumoniae (pneumococcus)
Adults: pneumonia, meningitis, septicaemia
Childr en: otitis media, sinusitus
Commonest cause of community-acquir ed
pneumonia, meningitis
Always in pairs: G+ve diplococci
Capsulated!
± Those with no spleen susceptible to pneumococcalinf ection
± Need vaccine (Meningitidis, Pneumonia, HI ±MPH)
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Viridans group str eptococci
Endocarditis!!
± Especially assoc. with I.E. following dental
procedur es
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Enterococcus faecalis
UTI (esp. in hospital)
± RF: IDC, instrummentation
Biliary tract inf ection Endocarditis
± Rar e, but lif e-thr eatening
±R
F:GI or urinary tractsurgery/instrummentation
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µMust know¶ Abx
Beta-lactams ± Penicillins: penicillin, amoxycillin/ampicillin, dicloxacillin/flucloxacillin,
piperacillin, ticarcillin
± Penicillin/beta-lactamase inhibitor combos: amoxycillin/clavulanate
± Cephalosporins: cephazolin, cephalexin, ceftriaxone, cefotaxime,cetazidime
± Carbapenems: meropenem Glycopeptides: vancomycin, teicoplanin
Aminoglycosides: gentamicin
Macrolides: erythromycin, roxithromycin, clarithromycin,azithromycin
Tetracylines: doxycycline
Antifolates: trimethoprim, co-trimoxazole Fluoroquinolones: ciprofloxacin, norfloxacin
Rifamycins: rifampicin
Nitroimidazoles: metronidazole
Others: fusidic acid, clindamycin
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Penicillin
Narrow-spectrum
Gram +ve bugsGram +ve bugs ± Str eptococci, enterococci, Clostridium spp. and other Gram +ve
anaerobes
N
o good if bug has be
ta-lactamase
No good against staphylococci
Phenoxymethylpenicillin (penicillin V): oral. ± No good for serious inf ections
Benzylpenicillin (penicillin G): par ental, IM, IV. ±
Drug of choice
for many inf ections
Procaine penicillin: IM only. ± Lasts 24hrs in bld, but only useful if organism is highly susceptible.
Benzathine penicillin: IM. ± Lasts 3-4wks in bld. Rheumatic f ever, syphilis!
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nti-staph
Flucloxacillin, Dicloxacillin (methicillin ± lab-use only)
StaphylococciStaphylococci Oral or IV
Fluclox: mor e likely cause cholestatic jaundice
Diclox: mor e irritating to veins if IV (thrombophlebitis)
MRSA«options: ± Glycopeptide (vancomycin, teicoplanin)
± Rifampicin + fusidic acid
± Rifampicin + ciprofloxacin (depending on susceptibility)
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M oderate-spectrum
Amoxycillin, ampicillin
Gram +veGram +ve, some Gramsome Gram ± ±veve ± E.g. E . coli, H . influenzae
Oral or par enteral ± Oral amoxycillin better absorbed
If EBV prominent r ed rash!
Broad-spectrum
Piperacillin, ticarcillin
P seudomonas aeruginosaP seudomonas aeruginosa cover, as well as Klebsiella spp.,enterococci
If using for Pseudomonas, need to add another anti-pseudomonas drug (pr eventr esistance)
Par enteral only
Can add beta-lactamase inhibitor
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P enicillin + beta-lactamase inhibitor
Amoxycillin + clavulanate (Augmentin®, AugmentinDuo Forte®)
Ticarcillin + clavulanate (Timentin®)
Piperacillin + tazobactam (Tazocin®) Even broader spectrum!
PROBLEM ± antibiotic-associated diarrheoa ± Clostridium difficile
± Normal flora in large bowel, but abx kill off all other N. flora
± µPseudomembranous colitis¶ ± Side eff ect of abx, or abx-assoc diarrhoea?
Stool sample, look f or C . difficile exotoxin
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Cephalosporins
1st generation
2nd generation
3rd generation
µ3rd ±and-a-bit¶ generation
Gram +ve
Gram ±ve
(& Gram +ve)
Gram +ve &
Gram ±ve
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1st generation ± µmoderate spectrum¶
Cephalothin, cephazolin, cephalexin
± Cephalothin, cephazolin = par enteral ± Cephazolin: longer half-lif e, less painful IM
± Cephalexin = oral
StrepStrep, StaphStaph, common Gcommon G ± ±veve e.g . E .E .
coli coli , Klebsiella sppKlebsiella spp.
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2 nd generation
M oderate spec + anti-Haemophilus
Cef aclor , cef uroxime (oral)
Better GBetter G ± ±ve cover ve cover , antianti--HaemophilusHaemophilus
M oderate spec + anti-anaerobe
Cef oxitin, cef otetan (oral)
± Cefotetan: longer half-lif e, once-daily
Anti-anaerobe .: good activity against Bacteroides fragilis
(metronidazole is still pr ef err ed for anaerobes)
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3rd generation
Broad spectrum
Cef otaxime, cef triaxone
CommunityCommunity--acquired enteric Gacquired enteric G ± ±veve, not so good G +ve.
No use against P seudomonas Good CSF penetration .: good for meningitis
Ceftriaxone pr ef err ed: longer half-lif e, less fr equent dosing
Broad spectrum + anti- P seudomonas
Cef tazidime, cef epime Most enteric GMost enteric G ± ±ve bacilli,ve bacilli, P seudomonas aeruginosaP seudomonas aeruginosa, G +ve, G +ve Choice depends on cost
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Carbapenems
Imipenem, meropenem, ertapenem
Broad spectrum!!Broad spectrum!!
G+veG+veGG ± ±veve includingincluding P seudomonasP seudomonas
anaerobesanaerobes ((Bacteroides fragilisBacteroides fragilis))
No use against MRSA, Burkholderia cepacia, Stenotrophomonasmaltophilia
Meropenem pr ef err ed: ± Longer half-lif e .: less fr equent dosing
± Less s/e
± Better CSF levels Imipenem ± cause seizur es!
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Glycopeptides
Vancomycin, Teicoplanin
Gram +ve, MRSA, MRSEGram +ve, MRSA, MRSE Good alternative for penicillin hypersensitivity
No use against G ±ve
S/e: nephrotoxicity Vancomycin monitoring:
± Take level 30min befor e next due dose (trough level)
± Give next due dose as charted
± Do NOT wait for level to r eturn
± HMO/RMO to be notified of level
± HMO/RMO to adjust inter val to next dose accordingly (e.g . if level toohigh, 12-hrly 18-hrly)
± Levels befor e every 3rd dose
Aim 15-20 trough levels (intermittent dosing)
Aim 20-25 if 24-hr infusion (essentially never trough level)
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Aminoglycoside
Gentamicin
GramGram ± ±ve, includingve, including P seudomonasP seudomonas
aeruginosaaeruginosa
s/e: nephrotoxic, ototoxic
± Befor e & During therapy: r enal f xn, auditory
function, vestibular function, drug levels ± Use depends on local susceptibility patterns
± Once-daily dosing: just as eff ective, less toxic
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Macrolides
Erythromycin, roxithromycin, clarithromycin, azithromycin
Gram +veGram +veatypicalsatypicals ((Legionella,My coplasma, C hlamy diaLegionella,My coplasma, C hlamy dia spp.)spp.)
Bordetella pertussisBordetella pertussis
CorynebacteriaCorynebacteriasomesome H. influenzaeH. influenzae
No use against G ±ve rods: enteric
Erythromycin: often GI upsets if oral. Painful if par enteral
Roxithromycin: pr ef err ed oral form. Less GI s/e! Clarithromycin, azithromycin:
± Longer half-lif e
± Better oral bio-availability
± Azithromycin: once-daily dosing
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Tetracyclines
Doxycycline, tetracycline
Broad spectrum:
G +ve, GG +ve, G ± ±ve,ve, My coplasmaMy coplasma,, C hlamy dia,C hlamy dia,
RickettsiaRickettsia spp., some spirochaetesspp., some spirochaetes Use in: acne, PID, community-acquir ed pneumonia
S/e: photosensitive rashnausea ± common (take with food!)
If pr egnant >18/52, br eastf eeding, childr en <8y/o: AVOID! Foetalteeth malformation, teeth staining
Doxycycline = pr ef err ed
± Once-daily dosing
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Antifolate (give supplement if Fo drops)
Trimethoprim, sulphonamides
Trimethoprim: use in UTI
Co-trimoxazole: use in UTI, PCP, prophylaxis of PCP,Listeria, Nocardia spp., Stenotrophomonoas maltophilia,
meliodosis, shigellosis, pr evention of cer ebraltoxoplasmosis in HIV, tr eatment of pertussis, pr eventionof pertussis
Can cause hyperkalaemia (esp. if used with drugs thatr etain K+, e.g . ACEi, spironolactone)
C/I:
± Folate deficient megaloblastic anaemia
± G6PD deficiency
± Renal failur e, Cr. Cl <15mL/min
± May worsen blood dyscrasia, e.g . neutropenia
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Fluoroquinolone
Ciprof loxacin, nor f loxacin
GG ± ±veve (just about all), incl.P seudomonasP seudomonas, some G +ve cocci,G +ve cocci,mycobacteriamycobacteria
± Similar spectrum as aminoglycosides
No good against str eptococci, anaerobes
NOT to be used 1st line for P seudomonas inf ection!
Cipro = ³gold-std´ f luoroquinolone ± oral and IV equally good
Norfloxacin ± Useful for GIT and urinary inf ections
± Not useful for inf ections of other sites
s/e
± Photosensitive skin rash ± CNS toxicity (e.g . nightmar es)
± Achilles tendon ruptur e
± Some interact with theophylline, caff eine
Fluoroquinolones should be r eser ved for µworst-case scenario¶ (if r esistant = we¶r e scr ewed!)
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Nitroimidazole
Metronidazole, tinidazole
AnaerobesAnaerobes! ± E .g . Clostridium spp., Bacteroides spp.
± Protozoa (Trichomonas vaginalis, Giardia lamblia, Entamoebahistolytica)
Metronidazole: oral + IV + suppositories.
± Rx of choice in Clostridium difficile diarrhoea (Abx-induceddiarrhoea)
± Intra-abdo sepsis: Triple Therapy: metronidazole + ampicillin +
gentamicin
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Others
Clindamycin
± G +ve aerobes, most anaerobes, Toxoplasma gondii , community-acquir ed, non-multir esistant MRSA inf ection of skin + soft tissue
Chloramphenicol ± Broad spec, incl. Rickettsia, Chlamydia spp.
± Topical: eye, ear inf ections
± Systemic use: only if no other alternatives!
± S/e: bone marrow hypoplasia (r eversible, dose-dependent), aplasia (irr eversible, dose-
independent, rar e), gr ey baby syndrome (neonates)
Fusidic acid ± Narrow spec. Highly active against Staph aureus, esp. rifampicin + fusidic acid combo
± Only systemic use
± S/e: nausea, high serum bilirubin (high doses), rhabdomyolysis, elevated CK (if taking statinsalso)
Nitrof urantoin ± UTI Rx + prophylaxis. NO USE OUTSIDE URIN ARY TRACT
± Serious toxicities!: polyneuropathy, pulmonary hypersensitivity, haemolysis, hepatitis
Linezolid ± Staphylococci, enterococci, str eptococci
± Role in MRSA, VRE tr eatment
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