Bugs & Drugs!

8/8/2019 Bugs & Drugs!

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Bugs & Drugs!

Catrina Huang

MED V 2009



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



µMust know¶ bugs

Gram +ve

± Cocci

±Bacilli

Gram ±ve

± Cocci

± Bacilli

Others



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



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



Gram +ve rods

Bacillus spp. ± B. anthracis

± B. cereus

Clostridium spp. ± C . tetani

± C . botulinum

± C . perfringens

± C . difficile

Corynebacterium diphtheriae

Listeria monocytogenes



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



Gram ±ve cocci (diplococci)

Neisseria meningitidis (meningococcus)

Neisseria gonorrhoeae (gonococcus)



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)



Gram ±ve rods

Enteric tract

Respiratory tract

Animal sources (zoonotic organisms)



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



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



G ±ve rods: Respiratory

Haemophilus influenzae

Bordetella pertussis

Legionella pneumophilia



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



G ±ve rods: Animal sources

P asteurella multocida

± Animal bites! Causes inf ection (cellulitis) of

bite wound

Brucella spp.

Francisella tularensis

Yersinia pestis



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



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?)



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



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



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



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)



Viridans group str eptococci

Endocarditis!!

± Especially assoc. with I.E. following dental

procedur es



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



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



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!



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)



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



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



Cephalosporins

1st generation

2nd generation

3rd generation

µ3rd ±and-a-bit¶ generation

Gram +ve

Gram ±ve

(& Gram +ve)

Gram +ve &

Gram ±ve



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.



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)



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



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!



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)



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



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



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



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



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!)



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



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

Bugs & Drugs!

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