Microbiology Flashcards
Mechanism of action of Antibiotics
Inhibit cell wall synthesis ------- β lactams(Penicillin, Cephlosporin, Carbapenems) ------- Glycopeptides (Vancoymycin, Teicoplanin) Inhibit protein synthesis ------- Aminoglycosides (Gentamicin) ------- Tetracycline (Doxycycline) ------- Macrolide (Erythromycin) ------- Chloramphenicol ------- Oxazolidinones (Linezolid) Inhibit DNA synthesis ------- Fluoquinolone (Ciprofloxacin) ------- Nitroimidazoles (Metronidazole) Inhibit RNA synthesis ------- Rifamycin (Rifampacin) Cell membrane toxin ------- Polymyxin (Colostin) ------- Cyclic lipopeptide (Daptomycin) Inhibit folate metabolism ------- Sulfonamide (Sulphamethoxazole) ------- Diaminopyramidines (Trimethoprim)
Differences in cell structure in Gram +ve and Gram -ve
Gram +ve have thick peptidoglycan cell wall
Gram -ve have thin peptidoglycan cell wall + outer membrane
Inhibit cell wall synthesis
- —– β lactams(Penicillin, Cephlosporin, Carbapenems)
- —– Glycopeptides (Vancoymycin, Teicoplanin)
Examples of βlactams
Penicillin ---- Benzylpenicillin Cephalosporin ---- 3rd gen: Ceftriaxone, Cefotaxime, Ceftrazidime ---- 2nd gen: Cefuroxime ---- 1st gen: Cephalexin Carbapenams ---- Meropenam
MOA of β lactams
Bind to penicillin-binding proteins –> ↓cell wall cross links –> weaker membrane –> lysed
Risk of cross-reactivity between βlactams
10%
Co-amoxiclav
Amoxicillin + Clavulanic acid
Tazocin =
Piperacillin (β lactam) + Tazobactam (β lactamase inhibitor)
With ↑generation of cephalosporin
↑Gram -ve cover, ↓Gram +ve cover
Why is Cef (cephalosporin) often given with Metronidazole
Met provides anerobe cover
ESBL stands for
Extended spectrum β-lactams
ESBL Tx
Carbapenam-sensitive
Resistant to Penicillin and Cephalosporins)
Carbapenemase
Resistant to Pencillin, Cephalosporin and Carbapenem
Inhibit protein synthesis
Inhibit protein synthesis (cATOM)
- —— Aminoglycosides (Gentamicin)
- —— Tetracycline (Doxycycline)
- —— Macrolide (Erythromycin)
- —— Chloramphenicol
- —— Oxazolidinones (Linezolid)
Example of Glycopeptides
Vancomycin, Teicoplanin
MOA of Glycopeptides
Bind to enzymatic target (peptidoglycan precursors) –> weakened cell wall –> lyse
Similar MOA in β lactams bt bind to substrate (precursors)
Nephrotoxic ABx
Gentamicin, Amikacin (aminoglycosides)
Example of Aminoglycoside
Gentamicin, Amikacin, Tobramycin
MOA of Aminoglycosides
Aminoglycoside binds to 30S ribosomal subunit to prevent causing misreading of dcodons along the mRNA–> inhibits protein synthesis
Example of Tetracycline
Doxycycline
MOA of Tetracycline
Binds to 30S ribosomal subunit to prevent aminoacyl-tRNA binding –> inhibits protein synthesis
Example of Macrolide
Azithromycin, Clarithromycin
MOA of Macrolide
Binds to 50S ribsomal subunit –> prevents binding of peptidyl-tRNA
MOA of Chloramphenicol
Binds to 50S ribsomal subunit –> Prevents formation of peptide bonds
Example of Oxazolidinone
Linezolid
Inhibit DNA synthesis
Inhibit DNA synthesis
- —— Fluoquinolone (Ciprofloxacin)
- —— Nitroimidazoles (Metronidazole)
MOA of Oxazolidinone
Binds to 23S component of 50S subunit to prevent formation of functional 70S initial complex
Example of Quinolone
Ciprofloxacin
MOA of Fluroquinolone
Bind to DNA gyrase –> inhibit DNA synthesis
Example of Nitroimidazole
Metronidazole, Nitrofurantoin (related)
MOA of Nitroimidazole
Under anerobic conditions, active intermediated is produced which causes DNA strand breakage
Inhibit RNA synthesis
Inhibit RNA synthesis
——- Rifamycin (Rifampacin)
Example of Rifamycin
Rifampicin
MOA of Rifampicin
Binds to RNA polymerase –> inhibits initiation –> Inhibits RNA synthesis
S/E organse secretions, Liver enzyme inducer
Cell membrane toxin
Cell membrane toxin
- —— Polymyxin (Colostin)
- —— Cyclic lipopeptide (Daptomycin)
Examples of cell membrane toxins + MOA
Daptomycin - inserts into cell membranes –> leak ions
Colistin –> unknown
Inhibit folate metabolism
Inhibit folate metabolism
- —— Sulfonamide (Sulphamethoxazole)
- —— Diaminopyramidines (Trimethoprim)
Example of Sulfonamide + MOA
Sulphmethoxazole –> interferes with folate metabolism
Example of Diaminopyrimidine + MOA
Trimethoprim –> interferes with folate metabolism
Co-trimoxazole =
Sulphamethoxazole + Trimethoprim
Mechanisms of ABx resistance
BEAT drug action
- Bypass ABx sensitive step in pathway (Trimethoprim)
- Enzymatic drug inactivation (β lactamase)
- ↓Accumulation of drug (Tetracycline resistance) - ↓uptake or efflux
- change drug Target (MRSA, Quinolone resistance)
β-lactamases - types, act against
Breaks down β lactams
- β-lactamase (against Penicillin)
- ESBL (against cephalosporins)
- AmpC (against cephalosporins, not inhibited by Clavulanic acid)
- Carbapenemase (against all β lactams)
MRSA - resistance mechanism
Altered target (mecA gene encodes novel PBP called PBP-2a)
Abx for ESBL
β-lactam + Aminglyocoside (Gentamicin, Amikasin)
ABx for MRSA
Vancomycin (or Linezolid)
Abx for C diff
Metronidazole (or Vancomycin)
Abx for Chlamydia
Doxycycline
ABx for bacterial conjunctivitis
Chloramphenicol
ABx for VRE
Linezolid
Daptomycin
Cover for anerobes
Metronidazole
ABx fo PCP
Co-trimoxazole = Trimethoprim + Sulphamethoxazole
ABx for UTI
Trimethoprim or Nitrofurantoin
ABx for Hospital UTI
Augmentin (or Cephalexin)
ABx for pseudomonas
Gentamicin, or Tazocin
Main ABx for S aureus
Flucluoxacillin
Main ABx for Skin infections
Flucluoxacillin +/- Vancomycin (if MRSA)
Main ABx for meningitis
Ceftriaxone +/- Amoxicillin (listeria cover)
ABx for pharyngitis
Benzylpenicillin (cover Group A strep)
ABx for CAP (mild)
Amoxicillin (cover Strep pneumoniae + Hib)
ABx for CAP (severe)
Co-amoxiclav + Clarithromycin
ABx for HAP
Amoxicillin + Gentamicin OR Tazocin
Abx for E. coli
Gentamicin
Define minimum inhibitory concentration
Least amount of drug required to inhibit growth of organism in culture
Assessed using agara disc diffusion (calculate from boundary of growing + inhibited growth)
Empirical ABx therapy
Use BSABx which is likely to cover the likely organisms
Then change based on culture sults to ↑specific/narrow agent
Pharmacokinetic/Pharmacodynamic ideal for Gentamicin
Peak above MIC (Cmax)
Pharmacokinetic/Pharmacodynamic ideal for Penicillin
Time above MIC
Causes of secretory diarrhoea (profuse, watery diarrhoea)
Vibrio cholera E coli (ETEC, ERPC, EHEC)
Causes of inflammatory diarrhoea (neutrophil in stools)
Campylobacter
Shigella
Salmonella (non-typhoidal)
EIEC
Causes of enteric fever (lymphocytes in stool)
Salmonella (typhoidal)
Yersinia spp
Brucella
Staphylococcus aureus
Aetiology: Pre-formed enterotoxin (exotoxin) –> superAg in GIT
Sx: Diarrhoea (non-bloody) and Vomiting
<6 hr incubation
Micro: Catalase +ve, Coagulase +ve, Gram +ve coccus, Clusters/Clonies, Protein A, β haemolytic on blood agar
Self-limiting
Bacillus cereus
Reheated rice --> spre germinate Microscopy: spore-forming Gram +ve rod Aetiology: Heat stable emetic toxin (remains after heating) + Heat labile diarrhoeal toxin (can be destroyed by heating) Sx: Watery diarrhoea (non-bloody) <6hr incubation Self-limiting
Clostridia botulinum
Gram +ve anaerobe
Canned/Vacuum packed food
Preformed toxin INACTIVATED by cooking (blocks Ach release from nerves)
Tx: Antitoxin
Clostrdia perfringens
Gram +ve anaerobe
Reheated meat
Watery diarrhoea +/- Vomiting (24 hours)
Incubation 8-16 hours
Clostridia difficile
Gram +ve anaerobe 2 toxins (A, B) Associated with ABx Ix: Pseudomembranous colitis Tx: (1) Metronidazole, Infection control (2) Vancomycin
Listeria monocytogenes
Outbreaks of febrile gastroneteritis
Refrigerated food, Unpasteruised diary, Vegetables
Microscopy: β-haemolytic, aesculin +ve, tumbling motility
Sx: Watery diarrhoea, Fever, Vomiting
Tx: Ampicillin or Ceftriaxone
Types of E coli
Diarrhoea +/- bloody (if haemorrhagic form) Faecal-ortal route Self limiting - ETEC - EIEC - EHEC - EPEC
ETEC
Toxigenic –> traveller’s diarrhoea
EIEC
Invasive dysentery
EHEC
Haemorrhage (shiga-like verocytotoxin) (Haemorrhagic 0157)
EPEC
Infantile diarrhoea (Paeds)
Salmonella typhi / paratyphi (enteric fever)
Constipation (slow onset) Rose spots Splenomegaly Anaemia, Leukopenia Fever Blood culture +ve Multiples in Peyer's patches Tx: Ceftriaxone
Salmonella enteritidis
Poultry, Eggs, Meat
Diarrhoea (non-bloody)
Self-limiting
Shigella
Shiga toxin –> affects distal ileum/colon
Fever
Bloody diarrhoea
Tx: avoid ABx
Vibrio cholerae
Rice water stool (with no inflammatory cells)
Enterotoxin A and B
Water contaminated with huan faeces
Tx: supportive
Vibrio parahaemolyticus
Raw undercooked seafood (in Japan)
Diarrhoea
Self-limiting
Tx: Doxycycline
Vibrio vulnificus
Water-bourne organism
Shellfish handler / Scuba diver
Fetal sepsis with D&V in HIV patients
Tx: Doxycycline
Campylobacter jejuni
Upasteurised milk, poultry Prodrome of headache + fever Bloody diarrhoea (foul smelling) Cx - GBS - Reactive arthritis Tx: Erythromycin
Yersinia enterocolitis
Food contaminated with animal faeces Prefers cold environment (4o) Enterocolitis Mesenteric adenitis Cx - Reactive arthritis - Erythema nodosum
Mycobacteria
HIV patients
Diarrhoea
Entamoeba histolytica
Mobile trophozoite found in diarrhoea MSM Food, water, soil Non-motile cyst in non-diarrhoea illness Histology: flask shaped ulcer Dysentery Flatuence Tenesmus Chronic weight loss Liver abscess Tx: Metronidazole
Giardia lamblia
Pear shaped trophozoite
Traveller / Hiker / MSM / Mental hospital
Ingesting cysts from faceally contaminated water
Non-bloody diarrhoea (foul smelling)
Flatulence
ELISA string test: string attached to ingested capules –> fished out
Tx: Metronidazole
Cryptosporidium parvum
Swimming
Oocysts seen in stool by modified Kinyoun acid fast stain
Severe diarrhoea in immunocompromised
Norovirus
Outbreaks
D&V
Cruse ships
Rotavirus
< 6 years old
Adenovirus
Type 40+41 –> non-blood diarrhoea
< 2 year olds
Immunocompromised
DDx Bloody diarrhoea
Shigella
Campylobacter
E coli
Hepatitis A transmission
Faecal-oral route (infected water)
RNA virus
Hepatitis A Serology
Anti-HAV IgM = recent infection
Anti-HAV = previous infection or vaccine
Hepatitis A disease course
↑ALT, ↑IgM
Later, ↑IgG
Hepatitis A - Tx
Supportive only
Hepatitis B - route of infection
dsDNA virus
Sexual
Vertical
Blood / needlestick
Hepatitis B - Ix
↑ ↑ALT, ↑AST
HBsAG (infection or vaccine)
HbcAb (acute IgM, chronic IgG)
Hepatitis B - Tx
PegIFN- α2a (direct anti-viral effect, upregulates MHC)
Tenofovir (RT inhibitor)
Lamivudine (inhibits viral polymerase)
Entecavir (inhibits viral polymerase)
Hepatitis C - route of infection
RNA virus
Blood products
Hepatitis C - Ix
ALT
Anti-HCV
Hepatitis C - Tx
PEG-IFN- α2b
Ribavirin
Hepatitis D
Only infect Hepatitis B +ve patients
Ix: IgM anti-HDV
Hepatitis E
RNA virus
Faecal-oral transmission
India
Tx: Supportive
Complications of Hepatitis B / C
Hepatitis –> Fibrosis –> Cirrhosis –> Cancer
↑ risk of Hepatocellular carcinoma
Liver transplant
uncomplicated vs complicated UTI
Complicated UTI has functional or structural abnormality (including: male, pregnancy, children, hospitalised)
Most common cause of UTI
E coli
Non E coli organisms causing UTI
Proteus mirabilis Klebsiella aerogenes Enterococcus faecalis Staphylococcus saprophyticus - only non-E-coli organism causing UTI in normal urinary stem Staphylococcus epidermis
Routes of UTI
Ascending UTI or Haematogenous route (bacteraemia, endocarditis)
+ve nitrite indicates
Likely UTI
-ve nitrite AND +ve leukocyte
Urine culture
Treat if symptomatic
Nitrites are specific for
Coliform bacteria (have a reducing enzyme converting nitrates –> nitrites)
Urine leucocytes indicate
Inflammation
Definition of UTI
> 10,000 CFU / ml + urinary symptoms
DDx sterile pyruia
Chlamydia, TB
Urine microscopy showing squamous cells
Perineal contamination
Treatment of UTI
Trimethoprim or Nitrofurantoin
Treatment of Pyelonephritis
Co-amoxiclav +/- Aminoglycoside (Gentamicin)
Tx of complicated UTI (pregnancy, male)
Cefalexin or Co-amoxiclav
Candida UTI is associated with
Indwelling catheter
Tx: removal will cure
CSF: ↑WBC polymorphs, ↑↑protein, ↓glucose, turbid CSF
Bacterial meningitis
CSF: ↑WBC lmphocytes, ↑/ protein, glucose
Viral meningitis
CSF: ↑ WBClymphocytes, ↑↑Protein, ↓Glucose
TB meningitis
Meningitis, Gram +ve diplococci, α-haemolysis
Streptococcus pneumoniae
Meningitis, Gram -ve diplococci
Neisseria meningitidis
Meningitis, Gram +ve rods
Listera monocytogenes
India ink stain, MSM
Cryptococcus
Meningitis organisms
Neisseria meningitidis (Gram -ve diplococci)
Streptococcus pneumoniae (Gram +ve diplococci)
In neonates
—- GBS
—- Listeria
—- E coli
TB
Viral: Coxsackie, Mumps, HSV2
Fungal: cryptococcus
Tx for meningitis
IV Ceftriaxone
Tx for encephalitis
IV Aciclovir
Define Hospital acquired infection
infection > 48 hr of admission, 3 days discharge of 30 days of surgery, not present on admission
How common are HAI?
8%
Most common HAI
Hospital-acquired pneumonia
C. difficile - Gram, RF, Ix, Tx
Gram +ve, spore-forming anerobe
Risk factors: ABx
Ix: Pseudomembranous colitis
Tx: Metronidazole
E. coli - Gram
Gram -ve rod
Resistant to β-lactamases
Surgical site infection organisms
MRSA
Coagulase -ve Staphylococcus
Water-associated organisms
Legionella
Pseudomonas
Mycobacteria
Most common pathogens involved in surgical site infections
S aureus (MSSA, MRSA)
Less common
- E coli
- Pseudomonas
Tx for surgical site infection
Flucluoxacillin
Septic arthritis - organisms
Staph aureus (46%)
Streptococci (22%)
Less common: E coli
Septic arthritis - Sx
Fever
Red, hot, swollen joint
Unable to weight bear
Septic arthritis risk factors
RhA | OA | IVDU | DM | Immunosupression | Trauma
S aureus strain –> produces Panton-Valentine Leucocidin (PVL)
Septic arthritis - Ix
Blood culture
Joint aspirate > 50,000 WBC/mm3
ESR, CRP
Imaging: effusion