c.J

Figure 15. Life cycle of Schistosoma

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ID 11 Infectious Disease Toronto Notes 2023

Ectoparasites

• scabies,lice

• see Dermatology, D33

Table 28. Important Exposures

Insect 8ites

Mosquito Plasmodium spp.(Malaria)

Dengue

Chikungunya

lymphatic filariasis (Elephantiasis)

West Nile encephalitis

Yellow Feyer

Japanese encephalitis

Zika

lick Borrelia burgdorlerULyme Disease)

Rickettsia rickeltsii ( Rocky Mountain Spoiled Fever)

Ityponosoma brucei spp.(African sleeping sickness)

Leishmonio spp. (leishmaniasis)

Bartonella bocillitormis (Bartonellosis)

Yersinia (Plague)

Tunga penetrans (lungiasis)

fty

Flea

Mammal Bites

Oog/Cal

Human

Oral Exposures

Unpasteurired Milk

Undercooked Meat/Fish

Water

Environmental Exposures

Freshwater

Rabies. Pasleurella.anaerobes.Streptococcus, S. aureus.8orlonellohenselae.letanus

Streptococcus. S.aureus,oral anaerobes,Eikenella

Brucella spp., non-tuberculous Mycobacteria,Salmonella,C. coli. Listeria

Enteric bacteria.helminths, protozoa (e.g. Toxoplasma)

Hepatitis A/E. Norovirus. cholera.Salmonella,Shigella, Giardia. poliovirus,Cryptosporidium.Cydospora

Leptospira spp.,schistosomes.Acanthamoeba, Naegleria fowled

Soil Hookworms. Toxocara spp.(visceral larva migrans). Leptospira interrogans(leptospirosis)

Adapted with permission Irorn lancet 2003:361:1459*1469

Travel Medicine

General Travel Precautions

•vector-borne:long sleeves, long pants, hats, insecticides (containing permethrin) applied to clothes,

belongings, and bed nets; and skin repellents (e.g.DHET,icaridin) applied to exposed skin

•food/water:avoid eating raw meats/seafood, uncooked vegetables, and milk/dairy products;drink

only bottled beverages, chlorinated water, boiled water

•recreation: caution when swimming in schistosomiasis-endemic regions (e.g. Lake Malawi),freshwater rafting/kayaking, beaches that may contain human/animal waste products, near storm drains,

after heavy rainfalls

•prophylaxis: malaria (chloroquine, mefloquine, atovaquone t proguanil, doxycydine), traveller'

s

diarrhea ( bismuth salicylate, rifaximin)

•standard vaccines up to date (hepatitis B, MMR, tetanus/diphtheria, varicella, pertussis, polio,

influenza)

•travel vaccines: hepatitis A /B, Japanese encephalitis, typhoid fever, yellow fever, rabies, ET'

EC, cholera

•sexually transmitted and blood-borne infections:safe sex practices, avoidance of percutaneous injury

through razors, tattoos, piercings

Infectious Diseases to Consider

•vector-borne: malaria, dengue fever, chikungunya, yellow fever,spotted fever rickettsioses, West Nile

virus, trypanosomiasis, Japanese encephalitis,tick-borne encephalitis, leishmaniasis, Zika virus,

filariasis

•sexually transmitted: HIV, HBV, acute HSV,syphilis, usual S

'

l

'

ls, e.g. gonorrhea and chlamydia

•zoonotic:rabies, hantavirus, tularemia, Q fever, anthrax, brucellosis, Ebola

•airborne:TB, measles, varicella

•food/water:HAV, HEV, brucellosis, typhoid, paratyphoid, amoebiasis, dysentery, traveller’s diarrhea,

cholera,Campylobacter spp.

•soil/water:schistosomiasis,strongyloidiasis, leptospirosis, cutaneous larva migrans, histoplasmosis,

paracoccidioidomycosis

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Fever in the Returned Traveller

Etiology

• commonly identified causes of fever in the returned traveller

parasitic:malaria (20-30%)

viral:non-specific mononucleosis-like syndrome (4-25%), dengue (5%), viral hepatitis(3%)

bacterial: typhoid from Salmonella (2-7%), rickettsioses (3%)

diverse group of causative pathogens:traveller’s diarrhea (10-20%),respiratory tract infection

(10-15%), UT1/STI (2-3%)

l

'

ever in a returned traveller from a malaria endemic area is considered malaria until proven

otherwise

• can be caused by routine infections that are common in non-travellers (e.g. UR'

TT, UTT)

• less commonly, fever can be due to non-infectious causes (e.g. DVT/PE, drug fever, inflammatory

disorder unmasked by travel-acquired infection)

History

• pre-travel preparation

• travel itinerary: when, where, why, what, who, how?

dates of travel (determine incubation period)

season of travel:wet or dry

destination: country, region (urban or rural), environment (jungle, desert, etc.)

purpose of trip

• persons visiting friends and family are more likely to be exposed to local population and pathogens

style of travel: lodgings, camping, adventure travelling

local population:sick contacts

• transportation: use of animals

• exposure history

• street foods, untreated water:increased risk of traveller'

s diarrhea, enteric fever

uncooked meat/unpasteurized dairy: increased risk of parasitic infection

• body fluids (sexual contacts, tattoos, piercings, IVDU, other injections)

increased risk of HBV, HCV, HIV, UC,C. trachomatis,syphilis

animal/insect bites:increased risk of malaria, dengue, rickettsioses, rabies

• fever pattern

• incubation period: use the earliest and latest possible dates of exposure to narrow the differential

diagnosis and exclude serious infections

• <21 d:consider malaria, typhoid fever, dengue fever, chikungunya, Zika, rickettsioses, traveller'

s

diarrhea, respiratory tract infections (e.g. 1L1, COV1D-19); exclude HBV, TB

• >21 d: consider malaria, TB,typhoid fever; exclude dengue fever, chikungunya, traveller’s

diarrhea, rickettsioses

• body systems affected: Cil, respirator)'

, CNS,skin

Investigations

• all travellers with fever should undergo the following tests

blood work:CBC and differential,liver enzymes, electrolytes, creatinine, thick and thin blood

smears x3(for malaria), blood C&S

urine:urinalysis, urine C&S if dysuria or other localizing signs

• special tests based on symptoms, exposure history, and geography

« stool:C&S,O&P

. CXR

« viral serology (hepatitis,HIV)

dengue serology for lgM, dengue PCR

Treatment

• empiric treatment if ongoing fever for 48-72 h and negative malaria smears and all cultures pending

• travelled to India,Southeast Asia:azithromycin ± doxycycline

• travelled elsewhere: ciprofloxacin ± doxycycline

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Table 29. Fever in the Returned Traveller

Incubation Clinical Manifestations

Period

Geography/ Pathogen Diagnosis

Timing

Illness Treatment

Blood smear (thick and Ihin) x3

Rapid diagnostic test (with smeai

or PCR confirmation)

Antigen detection PCR

Africa.India.

Central and

Sooth America.

Southeast Asia

Usually rural,

night-biting

mosquitoes

SoutheastAsia.

Caribbean

Usually urban,

day-biting

mosquitoes

Global but

mostly Indian

subcontinent

7-30 d to mo Fever and flu-like illness (shakingchills,

headache,muscleaches,and fatigue)

Nauseai'vomitmg and diarrhea

Anemia and jaunSce

Plasmodium falciparum: (severe) kidney

failure,seirures.menial confusion,

prostration,coma,death,respiratory failure

Sudden onset of fever,headache,retro-orbital Anti-dengue IgM positivity

pain,myalgias,and arthralgias

Leukopenia

Thrombocytopenia hemorrhagic

manifestations (rare in travellers)

Sustained fever 39S

-40 C (103M04:

F)

Abdominal pain,headache,loss of appetite,

cough,constipation

Malaria Artesunate (for severedisease)

* Malarone8

.doxycyclme.or

clindamycin

Quinine sulfate •doiycydine

or clindamycin

Chloroquine * primaquine

Plasmodium

falciparum

Plasmodium vim

P.maloriae

P.orole

P.knowlesi

oryr

Symptom relief:

Acetaminophen (avoid using

NSAIDs and ASA becauseof

antiplatelet properties)

Dengue Dengue viruses 3 d to 2 wk

1-4 PCR

3 to 60 d Stool,urine,or bloodculture

positive for

S.

Ifphi or 5. Paratyphi

Ouinolone antibiotic (e

_g_

ciprofloxarin).ceftriaxone,or

macrolide

Typhoid

(enteriefever)

Salmonella

enterica serotype

Ifphi or serotype

Paratyphi

Tick Typhus Sickettsia 1to 2 v/k Fever,headache,myalgia,spotted rash DoxycyCline

Eschar at site of tick bite

Thrombocytopenia

Elevated liver enrymes

Fever,cough,hemoptysis

Serology

Presence of classic tick eschar

Mediterranean.

South Africa.India

Global CXR Isoniasd (lNH).rifampin

(RIF),pyratinamide (PZA).

ethambutol (EMB) •Vitamin B6

18 M. tuberculosis Variable

Sputum culture and acid-fast slain

Nucleic Acid Amplification Test

(NAAT)

Atypical lymphocytes on blood

smear and positive heterophilic

antibody (monospol) test

RT-PCR

Serology

Mononucleosis Caribbean. 30 to 50 d

Central andSouth

America

EBVorCMV Malaise,fatigue,pharyngitis,

lymphadenopathy.splenomegaly

Acetaminophen or NSAIDs.

fluids

Rest,fluids,analgesics/

antipyretics (avoid NSAIDs

until Dengue ruled out),

condom use.avoidpregnancy

Zika Virus

Disease

Africa.Southeast Zika virus

Asia.South

America:

spreading

Unknown. Headache,malaise,myalgia,arthralgia,mild

likely 3 to12 d fever,rash,conjunctivitis

Fever of Unknown Origin

Table 30. Classification of Fever of Unknown Origin (FUO) - Temp >38.3°C/101°F on several

occasions Causes of Nosocomial FUO

B, C,D,E

Classical FUO Nosocomial FUO Neutropenic FUO HIV-associated FUO

Bacterial and fungal infections of

respiratory tract and surgical sites

Catheters (intravascular and urinary)

Drugs

Emboli

Neutrophil count

- 500 mlor HIV infections

Duration >4 wk for outpatients.>3

d for hospitatriedpatients

Diagnosis uncertain after 3 Diagnosis unceitainafter 3 d of Diagnosis uncertain after 3 d of Dagnosisuncertain after 3 d of

outpatient visits or 3 d inhospital investigation,including at least 2 investigation,including at least 2 investigation,including at least 2

or 1wk of intensive ambulatory dincubation of cultures

investigation

Duration >3 wk Hospitalized patient

Infection not present/incubating is expected to fall to that level

on admission in1-2 d

d incubation of cultures d incubation of cultures

Etiology of Classic FUO

• infectious causes(

-30%)

• TB:extrapulmonary (most common), miliary, pulmonary (if pre-existing disease)

• abscess:subphrenic,liver,splenic, pancreatic, perinephric, diverticular,pelvic, psoas

osteomyelitis

bacterial endocarditis (culture negative)

other:viral (CMY, EBY, HIV'), bacterial (brucellosis, bartonellosis),fungal (histoplasmosis,

cryptococcosis), parasitic (toxoplasmosis,leishmaniasis, amoebiasis,malaria)

• neoplastic causes (

-20%)

most commonly lymphomas (especially non-Hodgkin) and leukemias,multiple myeloma,

myelodvsplastic syndrome

solid tumours:renal cell carcinoma (most common),breast, liver (hepatocellular carcinoma),

colon, pancreas,orliver metastases

• collagen vascular diseases (

-

30%)

• SLH, RA, rheumatic fever, vasculitis (temporal arteritis, polyarteritis nodosa), juvenile RA,Still

disease

• miscellaneous (

-

20%)

drugs(e.g. anti-microbials, anti-arrhythmics), factitious fever

• sarcoidosis,granulomatous hepatitis, IBD

hereditary periodic fever syndromes (such as familial Mediterranean fever)

• venous thromboembolic disease: RE, DVT

• endocrine:thyroiditis,thyroid storm, adrenal insufficiency, pheochromocytoma

• unknown in 30-50% despite detailed workup

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Approach to Classic FUO

• careful and repeated history:travel, environmental/occupational exposures, infectious contacts,

medication history, immunizations,TB history,sexual history, past medical history, comprehensive

review ofsystems (includingsymptoms that resolved before interv iew)

• thorough physical exam:fever pattern, rashes (skin,mucous membranes),murmurs, arthritis,

lymphadenopathy,organomegaly

• initial investigations as appropriate

• blood work:CBC and differential, electrolytes, urea,Cr, calcium profile,liver enzymes, HSR,CRP,

ferritin, muscle enzymes,RF, ANA,serum protein electrophoresis (SPEP), blood film

• cultures:blood (x3sets), urine,sputum,stool C&Sand O&P, other fluids as appropriate

• serology: HIV, Monospot,CMV IgM,syphilis

• imaging:CXR, abdominal imaging

• if there are diagnostic clues from any of the above steps, proceed with directed exam, biopsies or

invasive testing as required,followed by directed treatment once a diagnosis is established

if no diagnosis with the above,consider empiric therapy vs.watchful waiting

without intervention:patientsthat remain undiagnosed despite extensive workup have good

prognosis

• immunocompromised hosts have increased susceptibility to infectionsfrom pathogensthat are

typically low virulence,commensal,orlatent

Infections in the Immunocompromised Host

Factors that Compromise the Immune System

• general:age (very young or elderly), malnutrition

• immune disease:HIY,malignancies, asplenia (functional or anatomic), hypogammaglobulinemia,

neutropenia

. DM

• iatrogenic: corticosteroids, chemotherapy, radiation treatment, anti-TNF'

therapy,other

immunosuppressive drugs(e.g.in transplant patients)

Table 31. Types of Immunodeficiency

Type Conditions Vulnerable To

Cell-Mediated Immunity HIV.Hodgkin,hairy cell leukemia,cytotoxic drugs.SCID,

DiGeorge syndrome

Latent viruses

Fungi

Parasites

Non-tuberculosismycobacterium (NTM)

HumoralImmunity CU,lymphosarcoma,multiple myeloma,nephrotic

syndrome,protein-losing enteropathy,burns,sidde cell

anemia,asplenia, splenectomy,selectiveIgdeficiencies. serotype lyphi,G8SI

WiskoU-Aldrich syndrome

Chemotherapy,myelodysplasia,paroiysmal nocturnal Catalase-producing organisms \Slaphylocoaus.

hemoglobinuria,radiation,cytotoxic drug therapy.C3or C5 Serratia.Mocantia.Aspergillus)

deficiencies,chronic granulomatous disease

Encapsulated organisms (1pneumoniae,H.

inllueiuae. M.meningitidis.Salmonella enterico

Neutrophil Function

Febrile Neutropenia

Definition

• fever (S38.3°C/101*ForS38.0°C/100.4°1

;

for SI h)

• neutropenia: ANC <1.0

• ANC (absolute neutrophil count)

= WBC x (%neutrophils + %bands)

• severe neutropenia:ANC <0.5

Pathophysiology

• decreased neutrophil production

marrow: infection, aplastic/myelophthisic anemia,leukemia, lymphoma,myelodysplastic

syndromes

• iatrogenic: cancer chemotherapy, radiation,drugs

• deficiencies: vitamin Bt:. folate

• increased peripheral neutrophil destruction

• autoimmune:Eelty’ssyndrome, SLE, antineutrophil antibodies

splenic sequestration

Epidemiology/Etiology

• most common life-threatening complication of cancer therapy

• 8cases per 1000 cancer patients per yr in the U.S.

• causative organism identified only 1/3of the time

• GN (especially Pseudomonas) historically most common

• GP more common now

• fungal superinfection if neutropenia prolonged or if concurrent antibiotic use (especially Candida,

Aspergillus)

• frequently associated with IV lines, mucosal or GI infection.Typhlitis (inflammation of cecum) is a

rare complication,but can lead toserious infection and poor outcomes

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ID-15 Infectious Disease Toronto Notes 2023

Investigations

• examine for potentialsites of infection:mucositis and line infections are most common

• do NOT perform DRE;examine perianal region for perianal abscess

• blood C&S (x2 sets), urine C&S, culture all indwelling catheter ports,± sputum C&S and

nasopharyngealswab for respiratory viruses,stool for C.difficile testing if diarrhea

• CBC and differential,Cr, urea, electrolytes,AST/ALT,total bilirubin, chest imaging (CXR or Cl )

Treatment

• most hospitals have their own specific protocol so check local guidelinesfirst (see l igurc 16 )

• prophylaxis against febrile neutropenia ( I N ) with granulocyte colony-stimulating factor (G-CSF)

and granulocyte-macrophage colony-stimulating factor (GM-CSE) decreases hospitalization without

affecting mortality (indicated if risk of l-

'

N >20% or if 1

;

N has occurred in a previous chemotherapy

cycle)

LOW RISK (fulfills all of the following)

•Tolerates P0

•Normotensive

•Solid tumour

•No comorbidities

•No change in mentalstatus

•Normal CXR

•Neutropenia lasting <10 d

Afebrile by d 3-5:

Home with POAbx Can use cipro P0 amos/clav P0 )

*

•

piperacillirvtazobactam

orcefepime

orceftaadime

ormipenem ormeropenem IV

HIGH RISK

•Does not meet low risk entena

anaerobic coverage if

•Necrotizing mucositis

•Abscess

•Abdo or pelvic infection

•Anaerobes by C&S

Afebrile by d 3-5 of

persistent neutropenia:

Optimize forC&S

rcsiits but mamain

broad-spectrun

coverage

•metronidazole IV/PO

•vancomycinif

•MRSA

•Catheter-related infection

•Severe mucositis

•Hx quinolone prophylaxis

Febrile through d3-5:

Consider empinc

antifungal therapy

vancomycin IV

+antifungal if

, *Persistentfeveratd 3-5

•Suspected or proven

fungal infection

+ amphotericin B

orvonconazole

orcaspofungin

Figure16. Example of treatment protocol forfebrile neutropenia

Infections in Solid Organ Transplant Recipients

• infection is a leading cause of early morbidity/mortality in transplant recipients

• infection depends on degree of immunosuppression

• common infections <1 mo post-transplant

donor-derived infections

bacterial infection of wound/lines/lungs, herpetic stomatitis

• common infections >1 mo post-transplant

• viral (especially CMV, EBV, VZV)

• fungal (especially Aspergillus,Cryptococcus,P.jirovecii )

• protozoan (especially Toxoplasma )

• unusual bacterial/mycobacterial infections (especially TB, Socardia,Listeria)

Prophylactic Vaccinations Given Before Transplant

• to all transplant patients:DTaP, pneumococcal, influenza, hepatitis A and B,COVTD-19

• in select patients: MMR, varicella, HPV, herpes zoster

Immune Reconstitution Inflammatory Syndrome

Definition

• a harmful inflammatory response directed against a previously acquired infection following a

recovery of the immune system

Etiology

• paradoxical worsening of a successfully or partially treated opportunistic infection

• new onset response to a previously unidentified opportunistic infection

• the majority of cases are in patients with advanced HIV or immunosuppressed patientsstarting

anti-retroviral therapy or discontinuing immunosuppressive therapy;sudden recover)'from an

immunosuppressive state towards a pro-inflammatory state directed towardssubclinical infection

resultsin fever and inflammation

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ID 16 Infectious Disease Toronto Notes 2023

•can occur in response to multiple infections

• Mycobacteria (tuberculosis, avium complex)

Cryptococcus

Pneumocystis

• Toxoplasma

. HBV and HCV

• herpes viruses(VZV reactivation, HSV,CMV)

|C virus(progressive multifocal leukoencephalopathy)

• Molluscum contagiosum

• COVID-19

•clinical features are dependent on the type and location of the pre-existing infection

•thought to be worse with quick increase in CD-I count and with lower pre-treatment CD-I count

•non-HIV conditions with documented immune reconstitution inflammatory syndrome (IRIS):solid

organ transplant recipients, post-partum women, neutropenic patients, anti-TNF therapy

Epidemiology

•in HIV-positive patientsstarting ART,IRIS reported to affect

-10%

Investigations

•IRISis a diagnosis of exclusion

•rule out drug reaction, medication non-adherence,drug resistance

Treatment

•continue ARV therapy in HIV-positive patients with mild-moderate symptoms, but consider

discontinuation ifsymptoms are life-threatening or potentially irreversible

•treat underlying infection; initiate treatment for some infections prior to ARV initiation

•considerstarting corticosteroids/ NSAlDs to decrease inflammatory response

A Simplified Look at Antibiotics

• general overview,see Table 33, ID49 for more details

Table 32.Antibiotics Overview

Class art Drags GP Anaerobes GN Atypicals Other

Streptococcus Staphylococcusspp. irderococrasspp. CtBUdle BoaBi|e.g Pseudomonas Legionella, feiefeis Qtany&i Syphilis

tmrknmntk

ft

'

inHuemoe ^

Uamydia

pneumoniae.

Hycopksma

S. MSSA MUSA £ £

beats beam

M.

tOttsefc saprophyheus meningrtiSs goaarrhoeae

SPA)

PHUCIUJKS

Peffiatotimy

fcekata» (W)

J

-

/Oral

anaerobes

except

Gram(-)e.g.

B. lragilis

ArvcifaW

Anoinlbc|74)

-

/Oral

anaerobes

BKCfl

Gram(-) e.g.

8.fragilis

Ctaaoia

-B-LACTAM COHSMATION AGEMTS

AnoooUu- / V

darJasate

Pipetaolm.

tarobadaa

V / J J

celtctotaetazoiadaa

/

CtPHAlOSPODIK (P01- V)

1st oerersboc: V J J

ceptclein:

cefazote.ceta*

oril

2ndgesterat»c

ceftriniK

cefpronl

3rd generatroc

cefodnei

cefotauae.

celtriaicee

3rd geseratroc

cettarrSoe

4th genetshoe:

tefeptoe

J J / V J

ri

LJ

V / /

+ >/ V

V >/ V

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ID17 Infectious Disease Toronto Notes 2023

Table 32. Antibiotics Overview

Class asdOnijs GP Anaerobes GN Atypicals Other

Bdettsia Chicmydio Syphilis

trochomotis

Streptococcus Stophytococws spp. [stcrxxcaspp. Ct&ficile Jfeosebeswft»W|e.g. Pseudomonas tesfonefc

CUm/dm

H.

inhuemoe ^

Wicon.

i MSSA MRSA £ 5.

fotcots fotdmo

I.

Klebsiello soprophyticus meong&dB gooorrhoeoe

spp-l

V y y Sill geccrabcc

ceftotHprcle

ceftarofare*

Anr-ogfycosifes

gectacKK

tobranjai

snikicr

y V

y /

MACB0U0ES

y y erythrocyte

danlbooyt

*

y y y y

FLUOSOCUIHOLOKES

y y oprcfloean

lenfloisai

monfloECE

/

y y y y y y y /

y y y y y y y / +/•

y /

y norfloECB

‘

spcct2c«cs

tederel pentcatis

|S&P) pccptyUns

y y y y /

CABBAPtitK$

y y y y y y y y y

y y y y y y y n /

*

rcp«c«a

ertep«ea y y y y /

TETUttCUIIES

y y y y y y y dciytytiffr

tebxjdK/

nirocyto

tigecydcr

y / y

y y y y y y y y y

OTHEBS

y y y v

'fao! »

/

(aot

m> Vtf)

MOCOOjtlE y

(oral

vancomycin for

cm

gastroenteritis

*

)

y y y y y feptoerjor

bnezokd y y y y y

metreodazote y y

Dir-jcTTfcr

IMP SMI

nilicfuartrc

y y y y

y y y

y y y y

y y y fosfocycr y y

y coltsbfi y y

* AvailableinCanada through theSpecial AccessProgram

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Antimicrobials

Antibiotics

Reasons for Combination Therapy

• Polymicrobial infection

• Empiric therapy pending culture

results

• Synergy for difficult to treat

pathogens (e.g.Enterococcus spp.

causing endocarditis)

• To prevent emergence of resistance

• empiric antibiotic therapy

choose antihiotic(s) to cover for most likely and lethal organisms for the type of infection prior to

obtaining laboratory results (usually reserved for serious infections)

• adjust antihiotic(s) based on C&S and clinical response

• if causative organism identified, use antibiotic to which organism is susceptible

• if causative organism not identified, re-evaluate need for ongoing antimicrobial therapy (and continue

with empiric antibiotic(s) if indicated)

TOXIC METABOLITES

•Metronidazole

CELL WALL

Penicillins

Cephalosporins

Carbapenems

•Glycopeptides

Bactericidal

Antibiotics

Bacteriostatic

RNA POLYMERASE Antibiotics

•Rifampin

"Very Finely “ECSTaTIC"

Proficient At

CCell MurOer"

Vancomycin Erythromycin (and

other macrolidcs)

Fluoroquinolones Clindamycin

Sulfamethoxazole

Aminoglycosides Trimethoprim

Cephalosporins Tetracyclines

Carbapenems Chloramphenicol

Metronidazole

DNAGYRASE

•Fluoioquinolones

Penicillin PROTEIN SYNTHESIS

•Nitrofurantoin

MS RIBOSOME

•Macrolides

•Lincosamides

Daptomycin

3DS RIBOSOME

•Aminoglycosides

•Tetracyclines

FOLIC ACID PATHWAY

•TMP/SMX

•Dapsone

•Sulfoxone

MYCOLIC ACID PATHWAY

•Isoniazid

•Ethambutol ©Stuart Jantzen 2012

Figure 17. Mechanism of action of antibiotics

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Table 33. Antibiotics

Class and Orugs Coverage Mechanism of Action Adverse Effects Indications Contraindications

CELL WALL INHIBITORS

Penicillins

Benryl penicillin

- penicillin GIY.IU'

- penicillin VPO

Mild tomoderately severe infections

caused by susceptible organisms including:

actinomycosis,streptococcal pharyngitis,

streptococcal skin and softtissue infections,

pneumococcalpneumonia, syphilis

GP eiceptStaphylococcus.

Enlerococcus.

N.meningitidis.

Oral anaerobes

Syphilis

Bactericidal: p-lactam Immediate aHergy (lgE):

inhibits cell wall synthesis anaphylaxis.urticaria

by binding penicillin

binding protein [PBP)

preventing cross-linking of sickness

peptidoglycan

Hypersensitivity to

penicillin

Late-onset allergy (IgG):

urlicana.rash,serum

Interstitial nephritis

Dose related tonicity:

seizures

Diarrhea

Aminopenicillin See above

- ampicillinIV

- amoiicillin PO (Amonil:

)

Same aspenicillin AND

Enterococcus

listeria

Some strains of:

H.influenzae,E. coli.K.

pneumoniae

See above Bacterial meningitis and endocarditis

(IV ampicillin),acute otitismedia (AOM),

streptococcal pharyngitis,sinusitis,acute

exacerbations of COPD. part of multidrug

therapy for H.pylori treatment,Lyme disease,

pneumococcalpneumonia. UII(amoxicillin

and ampicillin) for most enterococci and

susceptible GN pathogens

Bacterial infections caused by staphylococci

and streptococci including skin and softtissue infections

Hypersensitivity to

penicillin or B-lactam

antibiotics

Isoxazolyl penicillin See above See above

- clonacillin

methiciltin

- nafcillin

- oxacillin

piactamcombinations

- amoiicillin-davulanate

(Clavulin -.

Augmentin'

)

- prperacrllra'tazobactam

(Taaocin -)

-ceftolozanetazobactara

Methicillin-sensitive

Staphylococcus aureus)

streptococci

Hypersensitivity to

clonacillin or any

penicillin

p-laclamase produced by See above

certain bacteria inactivate

p-laclams

Lactamase inhibitors

prevent this process,

preserving antibacterial

effect of p-lactams

Same as penicillin AND

Staphylococcus

H.influenzae

Enterococcus

Anaerobes (oraland gut)

P.aeruginosa (piperacillintazobactam)

Ceftolozane.'

tazobactam

primarily used forresistant GN

Various p-lactamase producing bacteria,

amoncillin-clavulanale-sensilive bacteria

including URTI.sinusitis. AOM. skin and soil

tissue infections.UTI.and severe intraabdominal and pelvic infections

Ceftolozane-tazobadam used to treat

resistant GN infections

Hypersensitivity

to penicillinor

cephalosporin

History of amoxicillindavulale-associated

jaundice or hepatic

dysfunction

Cephalosporins

PO GP GN Bactericidal:p-lactam

inhibits PBP.prevents

cross-linking of

peptidoglycan.

less susceptible to

penicillinases

10% penicillinallergy cross- Skin and soft tissue infections,prevention of Hypersensitivity to

reactivity

IV

T cephalexin cefazolm

(Keflex - ) (Aocef

-)

Goal with the

exception of

Enterococcus

end MRSA

E coti.

Klebsiella.

Proteus. H.

influenzae

|not all

isolates)

More coverage See above

than1*

(includes

anaerobes)

surgical siteinfections (cefazolin);infections cephalosporinsor other

caused bysusceptible organisms (especially B-lactam antibiotics

Staphylococcus anti Streptococcus infections)

r cefmoiime Weaker See above

(Zinacef -) activity

cefoxitin than1‘

See above Upper and lower RTI,pneumococcal

cefuroirme pneumonia,softtissue infections

(Ceftin3 )

cefprozil

(Cefzil- )

3* cefuime

(Suprax'

l

ceftriaxone S aureus *

(Rocephin "

) streptococcal

cefotaxime coverage

(Claforan"

) (cefotaxime

ceftazidime and

(Fortaz -

) ceftriaione)

especially5.

pneumoniae

Broad coverage See above

(includes

Pseudomonas

for ceftazidime

*1%penicillin allergy cross- Community-acquired pneumonia (cefotaxime. Severe hypersensitivity

ceftriaxone),gonorrhea (ceftriaxone),

community-acquired bacterial meningitis

(ceftriaxone,cefotaxime),abdominal and

pelvic infections (cefotaxime or ceftriaxone in

combination wrth metronidazole),once-daily

administration makes ceftriaxone convenient

for outpatient IV therapy

Empiric therapy for febrile neutropenia

(TypeI)to other B-lactam

antibiotics

reactivity

only)

4° cefepime Broad

(Maupime 3 ) spectrum

Broad coverage See above

including

Pseudomonas

Broad coverage See above

(except

Pseudomonas)

See above See above

5° Ceftobtprole Broad

(Zevtara ) coverage

ceftarotine including

(Teflaro'

)- MRSA

See above Acute bacterial skin and skin structure

infections,community-acquired pneumonia

See above

Carbapenems

imipenem (Primaiin '

) GP eicept MRSA GNincluding

Pseudomonas

*

Enterobocter.

extended-spectrum

B-lactamases (ESBLs).

anaerobes

See above:does not cover See above

Enterococcus

GP exceptEnterococcus.MRSA GN See above

includingEnterobocter (but not

Pseudomonas),anaerobes

B-lactam inhibits PBP and Penicillin a lergy crossprevents cross-linking of reactivity

peptidoglycan

Ireatment of infections caused byGNB Hypersensitivity to

producing extended-spectrum B-lactamases, imipenem

serious infections causedby susceptible Lowers seizurethreshold

organisms

Seizures

r

meropenem (Merrem See above :

) See above Hypersensitivity to

carbapenems

See above See above:once-daily administration makes Hypersensitivity

it convenient for outpatient IV therapy

erlapenem (Invanz 3

)

to carbapenems

+

’Available in Canada throng

*

the Special AccessProgram

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ID50 Infectious Disease Toronto Notes 2023

Table 33. Antibiotics

Class and Drugs Coverage Mechanism of Action Adverse Effects Indications Contraindications

CELL WALL INHIBITORS

Glycopeptides

vancomycin (Vancocin 5 ) GP including MRSA, nolVRE

C.difficile if P0

Glycopeptide sterically Red Man syndrome

inhibits cell wall synthesis Nephrotoxicity

Ototoxicity

Thrombocytopenia

Severe or life-threatening GP infections,

patients with 0-lactam allergy

May only be taken orally for severe C.difficile

infection

Hypersensitivity to

vancomycin

Other

fosfomycin GN (some coverage for

Pseudomonas but lower

Inhibiting cell wall

synthesis at the

compared to fnlerobaclerales) initial step involving

and GP|includingfrrferococct/s) phosphoenolpyruvate

synthase

P0 - mild nausea,diarrhea P0 - uncomplicated urinary tract infections Hypersensitivity to

possible IV - complicated urinary tract infections, fosfomycin

nosocomial lower RTI.osteomyelitis;

bacterial meningitis

IV - hypokalemia,

hypernalremia,liver

function test abnormalilies

PROTEIN SYNTHESIS INHIBITORS (50S RIBOSOME)

Macrolides

GP except [nlerococcus

GN:Legionella.B. pertussis

“Atypicals":Cblamydophila.

Mycoplasma

Binds to SOS ribosomal G!upset

subunit inhibiting protein Acute cholestatic hepatitis

synthesis

Susceptible RTI.pertussis,diphtheria.

Legionnaires' disease,skin and soft tissue

infections

Hypersensitivity to

erythromycin

Concurrent therapywith

astemicole.terfenadine

erythromycin

(Erybid:

.Eryc;

)

Prolonged OT

'