33. Bacteriology π’ Flashcards
List some common bacterial virulence factors and include their function.
- Flagella β movement and attachment
- Pili β adherence factors
- Capsule β protects against phagocytosis
- Endospores β metabolically dormant forms of bacteria β they are heat, cold, desiccation and chemical resistant
- Biofilms β organised aggregates of bacteria embedded in a polysaccharide matrix β antibiotic resistant
Give examples of bacteria that possess the following virulence factors:
a. Capsule
b. Endospores
c. Biofilms
βa. Capsule
- S. pneumoniae
b. Endospores
- Lysinibacillus sphaericus
- Clostridium sporogenes
c. Biofilms
- Pseudomonas aeruginosa
- S. epidermidis
What are exotoxins?
A toxin released by a living bacterial cell into its surrounding
What are the five different types of exotoxin? Give examples of bacteria that produce such toxins.
- Neurotoxins
- Botulinum toxin
- Tetanus E
- Enterotoxins
- Infectious diarrhoea
- Vibrio cholerae
- E. coli
- Shigella
- Infectious diarrhoea
- Food poisoning
- Bacillus cereus
- S. aureus
- Pyrogenic toxins
- S. aureus
- S. pyogenes
- Tissue invasive toxins
- S. aureus
- S. pyogenes
- C. perfringens
What is an endotoxin?
This is the lipid A part of lipopolysaccharide that is found on the outer membrane of Gram-negative cells NOTE: so ONLY Gram-negative cells can produce endotoxins
Why can treating patients with Gram-negative infection sometimes worsen their condition?
Antibiotics can cause lysis of the bacteria meaning that the endotoxins are released into the circulation in large quantities This can trigger an immune response that leads to SEPTIC SHOCK
What is an outbreak?
A greater than normal or greater than expected number of individuals infected or diagnosed with a particular infection in a given time period, or a particular place, or both
How can an outbreak be identified?
- Surveillance
- Good and timely reporting systems are necessary
What was the 2011 E. coli outbreak in Germany caused by?
Enteroaggregative shiga toxin producing E. coli
What were the symptoms of infection by shigella producing enteroaggregative Escherichia coli?
- Gastroenteritis
- Haemolytic uraemia syndrome
- Acute renal failure
- Haemolytic anaemia
- Thrombocytopenia
What was special about the bacterial strain that caused by outbreak?
- The bacterial strain had acquired the ability to produce shiga toxin (through phagetransfer)
- Shiga toxin production is a feature of Enterohaemorrhagic E. coli(EHEC)
This produced a new strain called Enteroaggregative haemorrhagic E. coli (EAHEC)
- Shiga toxin production is a feature of Enterohaemorrhagic E. coli(EHEC)
Describe the structure of shiga toxin.
There is an A subunit that is non-covalently associated with a pentamer of protein B
Describe the action of shiga toxin.
- Subunit A is the enzymatically active domain
- Subunit B is responsible for binding to the host cell membrane
- Subunit A cleaves 28S ribosomal RNA in eukaryotic cells thus inhibiting protein synthesis
- Bacterial ribosomes are also a substrate for subunit A so it can lead to decreased proliferation of susceptible bacteria (e.g. commensal microflora of the gut)
How was the shiga toxin gene transferred between bacteria?
Bacteriophage
What is the important virulence factor in EAEC?
Aggregative adherence fimbriae (AAF) β this is required for adhesion to enterocytes
What type of bacterium is Legionella pneumophila and what is the route of infection?
- Gram negative rod
- It is transmitted through inhalation of contaminated aerosols
Which cells within the human host does L. pneumophila infect and grow inside?
Alveolar macrophages
What is the important virulence factor for L. pneumophila?
Type IV secretion system
What feature of Mycobacterium tuberculosis makes it more difficult to treat?
It has a mycolic acid outer membrane β this prevents normal antibiotics from getting into the cell
State three bacterial sexually transmitted diseases including the species of bacteria that cause the diseases.
- Chlamydia - Chlamydia trachomatis
- Syphilis β Treponema pallidum
- Gonorrhoea β Neisseria gonorrhoeae
What is a major consequence of Chlamydia in the developing world?
Blindness (due to eye infection)
How does N. gonorrhoeae establish infection in the urogenital tract?
It interacts with non-ciliated epithelial cells
What are the important virulence factors of N. gonorrhoeae?
- Pili
- Antigenic variation escapes detection and clearance by the immune system
What is the most commonly reported infectious GI disease in the EU?
Campylobacter jejuni
What is the route of infection of Campylobacter and Salmonella?
Ingestion of undercooked poultry
State some important virulence factors of Campylobacter jejuni.
- Adhesion and invasion factors
- Type IV secretion system
- Toxin
Which subset of the population has the highest incidence of Salmonella and Campylobacter infection?
Young children (0-4 years)
What is an important virulence determinant of Salmonella sp.?
Type III secretion system NOTE: Salmonella sp. can cause outbreaks whereas Campylobacter tends to be sporadic cases
What are the important virulence factors of Vibrio cholerae?
- Cholera toxin
- Type IV secretion system
- Fimbria
Explain how cholera toxin works.
- It has A and B subunits
- A is the active toxin
- B allows entry of the toxin into the epithelial cell
- The A subunit activates adenylate cyclase, thus increasing the production of cAMP
- The cAMP then binds to CFTR and causes Cl- efflux
- Water follows the ion movement so you get massive movement of water into the lumen of the intestine
Which subsets of the population are at risk of infection by Listeria monocytogenes?
Immunocompromised Elderly Pregnant and their foetus
What are some special features of Listeria?
They can enter non-phagocytic cells and cross tight barriers (e.g. BBB and maternal-foetal barrier)
Name some bacterial vector-borne diseases.
- Q fever
- Plague
- Yersinia pestis
List some vaccine-preventable diseases. Identify which are viral.
- Diphtheria
- Invasive pneumococcal infections
- Invasive meningococcal infections
- Pertussis
- Tetanus I
- Invasive Haemophilus influenzae
- Rabies
Measles * Mumps* Rubella* Polio*
Define the following: a. Antimicrobial b. Antibacterial c. Antibiotic
-
a. Antimicrobial
- Interferes with growth and reproduction of a microbe
-
b. Antibacterial
- Commonly used to describe agents that reduce or eliminate harmful bacteria
-
c. Antibiotic
- Type of antimicrobial that is used as medicine for humans and animals
What is a health-care associated infection?
Infections that occur after exposure to healthcare Infection starts >48 hours after admission to hospital
Why do health-care associated infections cost money to the healthcare system?
They increase the length of stay at hospital
List some medical interventions that can increase the risk of infection.
- Catheterisation
- Intubation
- Lines (e.g. central venous lines)
- Chemotherapy
- Prosthetic material
State some other factors that increase the risk of infection in the hospital setting.
Dissemination by healthcare staff Concentration of ill patients
What are the ESCAPE pathogens? Commonly associated with antimicrobial resistance
- Enterococcus faecium
- Staphylococcus aureus
- Clostridium difficile
- Acinetobacter baumanii
- Pseudomonas aeruginosa
- Enterobacteriaceae
- ESC are Gram-positive
- APE are Gram-negative
What is the main problem with the escape pathogens?
They are antibiotic resistant
What is the most frequent cause of bacteraemia by a Gram-negative bacterium?
E. coli
What does E. coli frequently cause?
UTI
Which antibiotics is E. coli resistant to in many countries?
Cephalosporins
Which antibiotics is E. coli still sensitive to?
Carbapenems
State the target proteins and the method of resistance to the following classes of antibiotics:
a. Cephalosporins
b. Carbapenems
c. Methicillin
d. Vancomycin
- a) Cephalosporins
- Target:
- Penicillin binding proteins (PBP)
- Resistance:
- Extended-Spectrum Beta-Lactamase (ESBL)
-
b. Carbapenems
- Target:
- PBP
- Resistance:
- Carbapenemase enzymes
- Target:
-
c. Methicillin
- Target:
- PBP
- Resistance:
- alternative target (PBP2A)
- which has low affinity for methicillin and can function in its presence
- alternative target (PBP2A)
- Target:
-
d. Vancomycin
- Target: peptidoglycan precursor
- Resistance: synthesis of a different peptidoglycan precursor
What are extended-spectrum beta lactamases encoded on?
Plasmid
What are carbapenemases encoded on?
Transposon
What types of infections does Klebsiella pneumoniae tend to cause?
- UTI
- Respiratory tract
Which group of patients are at risk of Klebsiella infection?
Immunocompromised
Which classes of antibiotics are Klebsiella widely resistant to?
- Cephalosporins, fluoroquinolones and aminoglycosides
- Carbapenem resistance in the US
Which group of patients are at risk of P. aeruginosa infection?
Immunocompromised
Which class of antibiotics is P. aeruginosa widely resistant to?
Carbapenems
What is the most important cause of antimicrobial resistant infection in the world?
MRSA
What is Enterococcus faecium widely resistant to?
Vancomycin NOTE: causes blood stream infections
What is a health-care associated infection?
Infections that occur after exposure to healthcare Infection starts >48 hours after admission to hospital
What is Enterococcus faecium widely resistant to?
Vancomycin NOTE: causes blood stream infections
What is the most important cause of antimicrobial resistant infection in the world?
MRSA
Which class of antibiotics is P. aeruginosa widely resistant to?
Carbapenems
Which group of patients are at risk of P. aeruginosa infection?
Immunocompromised
Which classes of antibiotics are Klebsiella widely resistant to?
Cephalosporins, fluoroquinolones and aminoglycosides Carbapenem resistance in the US
Which group of patients are at risk of Klebsiella infection?
Immunocompromised
What types of infections does Klebsiella pneumoniae tend to cause?
- UTI
- Respiratory tract
What are carbapenemases encoded on?
Transposon
What are extended-spectrum beta lactamses (ESBL) encoded on?
Plasmid
State the target proteins and the method of resistance to the following classes of antibiotics: a. Cephalosporins b. Carbapenems c. Methicillin d. Vancomycin
-
a. Cephalosporins
- Target: Penicillin binding proteins (PBP)
- Resistance: Extended-Spectrum Beta-Lactamase (ESBL)
-
b. Carbapenems
- Target: PBP
- Resistance: Carbapenemase enzymes
-
c. Methicillin
- Target: PBP
- Resistance: alternative target (PBP2A), which has low affinity for methicillin and can function in its presence
-
d. Vancomycin
- Target: peptidoglycan precursor
- Resistance: synthesis of a different peptidoglycan precursor
Which antibiotics is E. coli still sensitive to?
Carbapenems
Which antibiotics is E. coli resistant to in many countries?
Cephalosporins
What does E. coli frequently cause?
UTI
What is the most frequent cause of bacteraemia by a Gram-negative bacterium?
E. coli
What is the main problem with the escape pathogens?
They are antibiotic resistant
What are the ESCAPE pathogens?
Enterococcus faecium Staphylococcus aureus Clostridium difficile Acinetobacter baumanii Pseudomonas aeruginosa Enterobacteriaceae NOTE: ESC are Gram-positive APE are Gram-negative
State some other factors that increase the risk of infection in the hospital setting.
Dissemination by healthcare staff Concentration of ill patients
List some medical interventions that can increase the risk of infection.
Catheterisation Intubation Lines (e.g. central venous lines) Chemotherapy Prosthetic material
Why do health-care associated infections cost money to the healthcare system?
They increase the length of stay at hospital
Describe the distinctive features of:
a. Gram positive bacteria
b. Gram negative bacteria
c. Mycolic bacteria
- a. Gram positive bacteria
- Thick peptidoglycan cell wall
- b. Gram negative bacteria
- Outer membrane that contains lipopolysaccharide (LPS)
- c. Mycolic bacteria
- Outer mycolic acid layer
What is DNA gyrase?
- A type of topoisomerase (topoisomerase II)
- It releases tension in DNA and is important in unwinding DNA to allow protein binding required for DNA replication
What does RNA polymerase do?
Produces RNA from a DNA template
What is the key difference between ribosomes in eukaryotes and prokaryotes?
Eukaryote = 40S + 60S
Prokaryote = 30S + 50S
State two classes of drugs that interfere with nucleic acid synthesis and name the enzymes that they inhibit.
- Sulphonamides β inhibits dihydropterate synthase
- Trimethoprim β inhibits DHF reductase
Trimethoprim and sulfamethoxazole drugs are sometimes used together. What is this preparation called?
Co-trimoxazole
Name a group of drugs that interfere with DNA replication and state its targets.
Fluoroquinolones (e.g. ciprofloxacin) inhibits bacterial DNA gyrase and topoisomerase IV
Name a group of drugs that interfere with RNA synthesis and state its main target.
Rifamycins (e.g. rifampicin) β inhibits RNA polymerase
List 4 groups of drugs that interfere with ribosomes.
- Macrolides
- Aminoglycosides
- Chloramphenicol
- Tetracyclines
Describe how peptidoglycan is synthesized, transported to the cell wall and incorporated into the cell wall.
- A pentapeptide is created on N-acetyl muramic acid (NAM)
- N-acetyl glucosamine (NAG) associates with NAM forming peptidoglycan
- The peptidoglycan is then transported into the cell wall by bactoprenol
- The peptidoglycan is then incorporated into the cell wall by transpeptidase enzyme, which cross-links the peptidoglycan pentapeptides
Which groups of drugs interfere with peptidoglycan synthesis and how do they do this?
- Glycopeptides (e.g. vancomycin) β they bind to the pentapeptides and inhibit peptidoglycan synthesis
- This is used as a last resort for Gram-positive bacteria that are resistant to other antibiotics
Name a drug that interferes with peptidoglycan transport and state its target.
Bacitracin β this inhibits bactoprenol, hence preventing peptidoglycan transport
Name a class of drugs that inhibit peptidoglycan incorporation and explain how they do this.
Beta lactams β they bind covalently to transpeptidase, which inhibits peptidoglycan incorporation into the cell wall
What are the three subsets of beta lactams?
- Carbapenems
- Cephalosporins
- Penicillins
Name two drugs that interfere with cell wall stability and explain how they do this.
- Lipopeptides β disrupt Gram-positive cell walls
- Polymyxins β bind to lipopolysaccharide and disrupt Gram-negative cell membranes
List five mechanisms of antibiotic resistance and give a brief description of each.
-
Additional target
- the bacteria produce another target that is unaffected by the drug
-
Hyperproduction
- the bacteria increase the production of the target so the antibiotics are less effective (this is energy inefficient)
-
Altered target site
- there is an alteration in the drug target so that the drug is no longer effective
-
Alteration in drug permeation
- down regulation of aquaporins (responsible for allowing drugs into cells) or the upregulation of efflux systems
-
Production of destruction enzymes
- beta-lactamases hydrolyse the C-N bond in the beta-lactam ring rendering the beta-lactams inactive
What are penicillins G and V normally used to treat?
Gram-positive bacteria
Name two drugs that are relatively beta lactamase resistant.
Flucloxacillin and temocillin
Name a broad-spectrum antibiotic that must be administered with another drug to become resistant to beta lactamases. What is this other drug?
- Amoxicillin (no antibiotic resistance on its own)
- Clavulanic acid (beta-lactmase inhibitor)
What are the mechanisms of action of isoniazid and rifampicin?
- Isoniazid β inhibits mycolic acid synthesis
- Rifampicin β inhibits RNA polymerase
Why do gram + bacteria stain purple?
Because of the peptidoglycan cell wall, which is impermeable so it retains the blue stain.
Difference between the strep species hemolytic actions?
Beta: hemolyze fully Alpha: incomplete hemolysis, turn green (viridans). gamma: Donβt hemolyze at all
Differentiate between staph and strep presentation?
staph: cluster like grapes strep: chains or diclocci (pair up), donβt clump like staph
What is associated with Corynebacterium Diptheriae?
gray pseudo membrane
How do you differentiate between gram + and - on a gram stain?
gram + = purple gram - = red
Different structures of gram + and - bacteria?
bacillus= rod shaped coccus = sphere shaped spirillum = spiral streptococci -> cocci in chains staphylococci -> cocci in clusters
3 different staph species?
-staph aureus -staph epidermis (foreign bodies - cath, prosthetic valve) -staph saprophyticus (UTIs)
What does staph aureus look like on a gram stain?
It is bright yellow on sheep blood agar, and will coagulate positive with hydrogen peroxide (bubbles) this differentiates it from the other 2 staph species that are negative coagulants.
What are the Streptococcus species?
Strep. pyogenes (group A) strep. agalactiae (group B) strep. pneumoniae (pneumococcus) -> GPdiplococci strep viridans Enterococcus (group D)
Why is strep pneumo so virulent?
Because it is encapsulated so when you have no spleen you are at high risk for strep pneumo infections (also why immunocompromised, children, and elderly are at risk). -> this doesnβt have lancefield antigens either
What are the lancefield antigens
differentiates between the different groups of streptococci species. All have specific antigens -> group A, B Viridans (alpha hemo) and pneumo donβt have lancefield antigens
Where are common places for bacterial infections (staph and strep)?
skin (staph), soft tissue and bone
What are the 2 main classes of infection
local: face -> acne generalized (systemic)
What is a localized infection?
the organism enters the body and reaches the target site of infection -> then adheres to or enters host cells and multiplies at site of infection. Infection spreads within site (resp. tract or intestines). -the sxs of the illness appear - organism doesnβt spread through the lymphatic system or reach the bloodstream. The infection subsides due to host defenses (immunity) -> the agent is eliminated from the body and the infected cells are replaced and pt is cured!!
Explain a generalized infection?
the organism enters the body and reaches the target site of initial infection. The organism then adheres to or enters the host cells and multiplies at initial site of infection. The infection spreads within the site and to other sites via tissues, lymphatic system, bloodstream (bacterimia, viremia) and possibly other routes. -sxs of illness may appear -organisms infect other organs, tissues and cells -> more spread via bloodstream - sxs of illness become severe -host defenses eliminate organisms leading to cure or disease continues, possibly leading to irreversible damage or death.
What are 2 common localized infections?
cellulitis, and erysipelas
What are some potentially lethal infections?
-necrotizing fasciitis (flesh eating) -myonecrosis (gas gangrene or clostridial myonecrosis) -pyomyositis (abscess from bacterial infection of skeletal muscles)
Common staph infections
gram positive cocci, grape like clusters most are harmless and reside normally on the skin and mucous membranes MRSA: resistant to b-lactam antibiotics
What might MRSA be confused with?
a spider bite
How does coagulase differentiate the staph species?
coagulase + species (virulence) -> staph aureus (common nasal flora) coagulase - species - staph epidermidis (universal skin flora)
How might staph present in an infection?
stye (cordeolum) boils, carbuncles, furuncles sinusitis hematogenous spread (IV -epid.) endocarditis pneumonia, emesis, impetigo, diarrhea, TSS, UTI, cystitis, osteomyelitis, SSSS
What are the cutaneous infections of S. aureus?
folliculitis (boils), furuncles, burns and wounds
What are deep infections of S. aureus?
osteomyelitis, abscesses, pneumonia, endocarditis, septicemia
What are the toxic mediated infections of S. aureus?
-staphylococcal scalded skin syndrome (SSSS), TSS, food poisoning
What are the most common skin and soft tissue infections of s. aureus? Who are they most common in?
Most common in immunocompetent host -abscesses (cutaneous -> common) -folliculitis -mastitis -wound infections - infect. IV catheter sites
What are other common staph aureus infections? (more severe)
bacteremia, septicemia, endocarditis, pneumonia, musculoskeletal: septic arthritis (injury)
Differentiate b/t the different associated MRSAβs
HA-MRSA: health care assod, occur in people that have been in hospitals. Usually assod with invasive procedures or devices CA-MRSA: community associated among healthy people. Can begin as a painful skin boil. Spread by skin-skin contact, At risk pop: high school wrestlers, child care workers, and people who live in crowded conditions
Process of MRSA infection
generally start as small red areas that resemble spider bites, boils, pimples that can quickly develop into deep, painful abscess that require surgical draining (Really rapid -> in 24 hours will progress) Sometimes will go deeper into tissue and cause life threatening infections in the bones, joints, blood stream, heart valves and lungs
Treatment process of MRSA
culture and sensitivity - septra or -Doxy
If MRSA + -> what do you do to rid yourself of infection?
Bactroban -> ointment in nose qd full body wash -Hibiclens: rule of 3: 3x a day for 3 days then 3 x a week for 3 weeks
Difference b/t strep cellulitis and staph cellulitis?
Group A strep cellulitis: follows an innocuous or unrecognized injury, inflammation is diffuse, spreading along tissue planes Staph aureus: usually assod w/ wound or penetrating trauma, localized abscess become surrounded by cellulitis
Tx of cellulitis
Donβt use Keflex -> doesnβt cover MRSA -now half of cellulitis infections are resistant to tx with kefex -Current tx: clindamycin, doxycycline, Bactrim, Septra
What is the DOC of cellulitis
Bactrim alt: clindamycin (sulfa allergy) Vanco: MRSA severe cellulitis: IV abx especially if pt has high fever and appears ill - be aggressive with tx!
What is the admission criteria for cellulitis?
animal bite on ptβs face or hand area of skin involvement >50% of limb or torso, or >10% of bod surface -coexisting morbidity (diabetes, Heart failure, renal failure, edema) -compromised host -need for IV Abx
What is an abscess?
when the tissue in the area of cellulitis turns to pus under the surface of the skin, the collection of pus is called an abscess -the pus is just dead, liquified tissue, billions of WBCs - the most common bacteria in the abscess is staph aureus - but many other bacteria can cause abscesses -The organisms kill the local cells resulting in the release of cytokines which trigger an inflammatory response which draws large numbers of WBCS -
What must abscesses be distinguished from?
empyemas -> these are accumulations of pus in a preexisting rather than a newly formed anatomical cavity
Clinical features of superficial, and deep seated infections?
superficial: skin and subcutaneous tissues -> infections of the hand Infections of the head and neck: suppurative parotitis (acute infection of the parotid) -Deep seated infections: hepatic abscess/ splenic abscess/ sub-phrenic abscess/ rectal abscess
When would you I and D? What is other part of tx of this?
Only if you see that there is an obvious abscess - should be drained + abx maybe - if the abscess has a lot of cellulitis around it then an abx is probably needed. -Antibiotics canβt penetrate w/o drainage so they need to be drained.
What is necrotizing fasciitis?
this is caused mostly from strep - it is when the bacteria in a cellulitis or abscess starts spreading quickly between the fat layer and the muscle underneath -necrotizing= living flesh to dead flesh - fasciitis means the infection is spreading along space b/t fat and muscle -the infection cuts off blood supply to the tissue above it and the tissue dies - the bacteria may also enter the bloodstream.
Tx of necrotizing fasciitis
cut all the dead tissue out, and keep cutting until only living tissue is left. -do this over and over again until the infection stops spreading. -Antibiotics help but donβt cure the infection -The open muscle needs to be tx like a burn with skin grafts - empiric abx to cover anaerobes, gram -, streptococci, and staph aureus -abx for min. of 3 weeks
What is myonecrosis?
Gas gangrene - pure clostridium perfringens infection -gas in gangrenous muscle group - incubation hours to days -local edema and pain accompanied by fever and tachycardia -discharge is sero-sanguinous, dirty, and foul, crunchy upon palpation
Tx of myonecrosis
Pen G or chloramphenicol -surgical removal of infected muscle -watch out for diabetics -consider hyperbaric chamber
What is pyomyositis
- mostly caused by staph aureus - a purulent bacterial infection of skeletal muscles which results in pus-filled abscess. - most common in tropical areas, temperate zones - mainly a disease of children 2-5 Tx: must be drained surgically and abx given for min. of 3 weeks
What are the staph toxin disorders?
Gastroenteritis (food poisoning) TSS Toxic epidermal necrolysis (TEN) - this started as rxn to drug -> SJS -> TEN Staph scalded skin syndrome (SSSS)
SSSS
also known as Ritter disease: causes by epidermolytic toxins produced by certain strains of staph. This toxin is distributed systemically and results in dissolution of keratinocyte attachments in only the upper layer of the epidermis. - Usually affects newborns and children, adults less affected b/c of improved renal fxn allows for clearance of toxins from the body (w/ renal failure = more susceptible)
Staph epidermidis infections occur when?
Staph epidermidis is a major component of the skin flora. - it is common in nosocomial infections: device/implant associated infections -> shunts, catheters, artificial heart valves, joints, pacemaker (anything foreign in the body) (endocarditis)
Strep infections
30 species of bacteria - gram + cocci in chains subdivided by ability to lyse RBCS: beta (complete lysis), alpha (partial lysis), gamma (no hemolysis)
What is erysipelas?
acute streptococcus infection of the upper dermis and superficial lymphatics. Caused most by strep. pyogenes (group A Beta hemolytic ) -Rarely caused by beta hero of B, C, G group - pathogen enters through a break in the skin and eventually spreads to the dermis and subcutaneous layer - can remain superficial or become systemic
General features and differences of cellulitis and erysipelas?
Varying degrees of skin or soft-tissue erythema, warmth, edema and pain -associated fever and leukocytosis -hx of trauma, abrasion, or skin ulceration Cellulitis has an ill-defined border that merge smoothy with adjacent skin, usually pinkish to red erysipelas: has an elevated and sharply demarcated border with a fiery-red appearance
Management of Cellulitis and erysipelas
local care: immobilization, elevation to reduce swelling, draw lines on areas to assess response to tx - 2 weeks of abx therapy: PCN or dicloxacillin
Impetigo
(pyoderma) -> superficial lesions that break and form highly contagious crust, often occurs in epidemics in school children, bug bites, poor hygiene, and crowded living situations
Differentiate between non-bullous and bullous impetigo?
Non bullous: strep Group A or it could be staph aureus - see in pre-school and young school age, very thin walled vesicle on erythematous base, transient, yellowish-brain crusts (thick Bullous (blister forming): staph aureus cause, all ages, bull: 1-2 cm, persist for 2-3 days, thin and flat, brownish crust, fluid filled
Predisposing factors to impetigo
malnutrition, diabetes, immuno-compromised status
complications of impetigo
strep infection (pink eye, meningitis, endocarditis) - scarlet fever (strep pyogenes (group A): get strawberry tongue - urtricaria - erythema multiforme: usually follows an infection or drug exposure
Tx of impetigo
usually dx by presentation - no cultures usually needed - first soak affected area in warm water or use wet compress to help remove overlying scabs - abx creams or ointments: bactroban AAA Fusidic acid cream AAA retapamulon ointment consider septra/bactrim if hx of MRSA
Common infections of strep progenies (group A beta hemolytic strep)
- cutaneous infections - pharyngitis (sore throat) - otitis media - sinusitis -pneumonia - streptococcal TSS Complications of GABHS: rheumatic fever glomerulonephritis
Describe the long term complications of Group A infections
rheumatic fever: follows overt or subclinical pharyngitis in children, extensive valve damage possible, arthritis, chorea, fever acute glomerulonephritis: nephritis, increased BP, occasionally heart failure, can become chronic leading to kidney failure
Signs of strep throat?
red, beefy tonsils that are covered in exudate, strawberry tongue, petechiae Differential: mono
Beta hemolytic group B strep
normal flora in lower GIT, female genital tract -pathogenicity: neonatal meningitis and sepsis and pneumonia meningitis in babies: wonβt eat, crabby -> fever, vomiting: Emergency
Strep pneumoniae (pneumococcus)
gram + cocci in pairs: pneumonia, otitis media, sinusitis, meningitis Prevention: vaccination (capsular antigens) immunization!!! sxs of strep pneumonaie pneumonia -> shaking, chills, rust colored sputum, consolidation in lungs
Otitis media
presence of a middle ear infection acute otitis media: occurrence of bacterial infection w/in the middle ear cavity otitis media w/ effusion: presence of non purulent fluid w/in middle ear cavity -> have bulging, taut, inflexible TM (have effusion: add decongestant to abx -> drain better) *OM: is 2nd most common clinical problem in childhood after URI
Epidemiology of otitis media
peak incidence in 1st 2 years
Acute otitis media facts
more common in boys -lower socioeconomic status (smoking) -seasonal disease (peak in Jan, Feb) - corresponds to rhinovirus, RSV, influenza seasons ( secondary infection to virus, donβt get good drainage from initial infection, immunity down)
RFs for acute otitis media
young age, bottle feeding, drinking a bottle in bed, parental hx, sibling hx, second hand smoke, daycare
etiology of acute otitis media
suppurative infection of middle ear cavity, common bacterial pathogens achieve access through blocked eustachian tube (infection, pharyngitis, pr hypertrophied adenoids) - air trapping -> neg. pressure -> bacterial reflux bacterial reflux + obstructed flow = effusion
organisms that cause otitis media
strep. pneumo H. influenza Moraxella catarrhalis Group A strep staph aureus pseudomonas aeruginosa RSV assoc. w/ acute otitis media
Signs and sxs of otitis media
sxs are often nonspecific: fever, irritability, poor feeding, otalgia, otorrhea, signs of common cold
What will you see on the physical exam if pt has otitis media?
erythematic, opaque (not translucent, bulging TM w/ loss of anatomic landmarks including a dull/absent light reflex otoscopy: decreased tympanic membrane motility (pulled tight)
Complications of otitis media
hearing loss, acute mastoiditis, chronic perforation of TM, tympanosclerosis, cholesteatoma, chronic suppurative OM, cholesterol granuloma: blue drum syndrome, facial nerve paralysis even worse: intracranial complications, bacterial meningitis, epidural abscess, brain abscess, subdural empyema, otitic hydrocephalus, lateral sinus thrombosis
Tx guidelines for otitis media
infants 102) observation period is an option
tx of otitis media
amoxicillin for 10-14 days or augmentin + auralgan (analgesic/adjunct for ear pain -> drops) TID
2nd line tx for otitis media
cefzil (2nd gen cephalosporin) 6 months to 12 years pediazole (erythro/sulfisoxazole) bactrim *used as secondary agents if the pt is allergic to pcn or primary abx has failed after 10 days and sxs persist
Streptococci viridans
alpha or gamma hemolytic -common oral/pharyngeal flora (bind to teeth, cavities) infections: endocarditis, bacteremia, and septic shock
Group D streptococci (enterococcus)
-UTI -endocarditis -intraabdominal infections (abscesses) -biliary tract infections -wound infections *resistant to vanco and ampicillin, even becoming resistant to aminoglycosides
Dx of streptococcal infections
- culture - ASO titers/streptozyme (body will develop abs to strep -> streptolysin O) - rapid Group A strep tests -gram stains antistreptolysin O (ASO) titer is a blood test to measure abs against streptolysin O, a substance produced by group A streptococcus bacteria
DOC for streptococcal infections
S. pyogenes: PCN (low incidence of resistant organisms S. pneumoniae: increased PCN resistance Erythromycin for both in PCN allergic pt Ampicillin for enterococcus
What is anthrax?
gram positive spore forming bacterium Bacillus anthracis (special capsule to avoid phagocytosis) - anthrax spores are easily found in nature, and can be produced in the lab, can last a long time in the environment - anthrax has been used before as bioterrorism agent - can be released into powders, sprays, food and water - primarily disease of herbivores which are infected by ingesting spores in the soil -natural transmission to humans by contact with infected animals or contaminated animal products
epidemiology of anthrax
reservoir: herbivores (cattle, goats, sheep), capable of surviving in enviro for prolonged periods Transmission: contact, ingestion, or inhalation of infective spores sources of infection: contaminated hides, wool, hair, bone, meat, or other animal products
Clinical features of anthrax
incubation period: 1-7 days (1-60 days) - clinical syndromes: cutaneous ulcer, respiratory, gi, oropharyngeal - inhalation anthrax= main threat spores may germinate up to 60 days after exposure - bronchopneumonia not a component -> hemorrhagic lymphadenitis and mediastinitis - hard to early dx
Cutaneous anthrax
stays local, necrotic center
inhalation anthrax epidemiology and clinical sxs
epidemiology: sudden appearance of multiple cases of severe flu illnesses with fulminant course and high mortality non-specific prodrome of flu-like sxs -possible brief interim improvement -abrupt onset of resp failure and hemodynamic collapse 2-4 days after initial sxs, possible accompanied by thoracic edema and widened mediastinum on CxR (from bleeding)
Diagnostic studies, microbe and pathology of inhalation anthrax
dx studies: chest radiograph w/ widened mediastinum, periph blood smear w/ gm + bacilli on unspun smear Micro: blood culture growth of large gm + bacilli with preliminary identification of Bacillus sp. patho: hemorrhagic medistinitis (death), hemorrhagic thoracic lymphadenitis, hemorrhagic meningitis
prophylaxis anthrax control
prophylaxis: pre-exposure: vaccine (not available?) post exposure: cipro or other quinolone or doxy (vaccine if available) CDC isolation: standard contact isolation if cutaneous lesions present
treatment of anthrax
prophylaxis: cipro or doxy x 60 days tx for cutaneous: cipro or doxy x 60 days tx for inhalation: cipro or doxy plus vanco, imipenem (initial rx= IV then switch to PO for total 60 days) same tx for children and pregos
Diphtheria
gram + rod -acute bacterial respiratory infxn caused by Corynebacterium diphtheria -may involve any mucous membrane: will see gray pseudomembrane - classified based on site of infection (laryngeal, cutaneous, ocular, genital) -very rare in 1st world countries
Most common complications of diphtheria
myocarditis and neuritis - death occurs in 5-10% from respiratory disease
symptoms and findings of Diphtheria
sxs: sore throat, malaise, cervical lymphadenopathy, and low grade fever - earliest pharyngeal finding is mild erythema, which can progress to isolated spots of gray and white exudate. In 1/3 of pts - elaboration of toxin induces formation of coalescing pseudomembrane. This membrane adheres tightly to underlying tissue and bleeds with scraping but doesnβt scrape off.
Tx of diphtheria
abxs: erythro or PCN G diphtheria antitoxin for severe cases - careful airway management -serial electrocardiograms and cardiac enzymes - neuro status should also be monitored carefully
What type of bacteria do you find in the small intestine?
Gram-negative
Give some examples of bacteria and viruses that use the upper respiratory tract as a portal of entry.
Neisseria meningitidis Influenza Parainfluenza Streptococcus pneumoniae Streptococcus pyogenes Staphylococcus aureus
Give some examples of intrinsic bacteria that can infect via the urogenital tract.
E. coli Klebsiella Candida
Give some examples of extrinsic bacteria that can infect via the urogenital tract.
Chlamydia Syphillis Neisseria gonorrheae
Give examples of bacteria that can infect via broken skin.
Staphylococcus aureus Streptococcus pyogenes
State some consequences of infection via broken skin.
Abscess formation Bacteraemia Necrotic infection
Give some examples of bacteria and viruses that infect via the gastrointestinal tract.
Vibrio cholera Salmonella Listeria Shigella E. coli Campylobacter jejuni
What are some consequences of infection via the gastro-intestinal tract?
Diarrhoea Bacteraemia/systemic infections
What two main factors affect pathogenecity?
Infectivity and Virulence
Define infectivity.
The ability of a pathogen to establish infection
Define virulence.
The ability of a pathogen to cause disease
Define infectious dose.
Number of bacteria needed to cause infection
Describe how vibrio cholerae causes disease.
It uses its flagella to propel itself into the mucosal membrane of the intestines. It then begins producing toxins A and B, which bind to GM gangliosides and triggers production of cAMP This leads to chloride efflux and hence movement of water into the lumen from the cells
State whether each of the following are Gram-positive or Gram-negative:
Shigella - negative Streptococcus - positive Listeria - positive Clostridium - positive Vibrio cholerae - negative E. coli - negative Salmonella - negative Staphylococcus - positive Neisseria - negative Haemophilus influenzae - negative
Give two examples of Gram-negative opportunistic bacteria.
Pseudomonas aeruginosa Acinetobacter baumanii
Give two examples of Gram-positive opportunistic bacteria.
E. faecalis Staphylococcus epidermidis
What is the difference between Gram-negative and Gram-positive bacteria?
Gram-negative bacteria have a thin peptidoglycan layer with two membranes (cytoplasmic and outer membranes) Gram-positive bacteria have a thick peptidoglycan layer, which retains the dye well. It only has one membrane
Give examples of some Gram-negative pathogenic bacteria and the diseases they cause.
E. coli β diarrhoea, dysentery, kidney failure Salmonella - food poisoning, typhoid Shigella β dysentery Neisseria β meningitis + gonorrhoea Vibrio cholerae - cholera
What feature is found only on Gram-negative cell walls?
Lipopolysaccharide
Give examples of some Gram-positive pathogenic bacteria and the diseases they cause.
Staphylococcus aureus β skin infections, endocarditis, bacteraemia, pneumonia Streptococcus pneumoniae β pneumonia, meningitis, otitis media Streptococcus pyogenes β tonsillitis, necrotising fasciitis, scarlet fever
Give examples of some Mycobaceria and the diseases they cause
Mycobacterium tuberculosis β TB Mycobacterius leprae - leprosy
What is another way of classifying bacteria?
Intracellular and Extracellular pathogens
Give examples of some extracellular pathogens.
Staphylococcus Streptococcus Neisseria Yersinia
What are the three methods by which bacteria survive in the host cell?
Escape Preventing fusion with lysosome Surviving in the phagolysosome
Give examples of bacteria that survive using each of the above methods.
Escape β Listeria, Shigella Prevent fusion of lysosome β Salmonella, Mycobacteria, Chlamydia Survive in phagolysosome - Coxiella
Motility and Invasion require which two multi-protein machines?
Flagella Type III Secretion system
Describe the role of the type III secretion system.
A protein machine assembles which provides a channel through which virulence proteins can be injected into the host cell The virulence proteins then stimulate actin polymerisation and membrane ruffling which allows bacterial internalisation Gram-positive bacteria donβt have the type III secretion system
Describe another way in which actin is manipulated by bacteria.
Bacteria (such as listeria and shigella) can polymerise actin at one pole of the bacterium forming comet tails This polymerisation propels the bacterium through the cytoplasm
What are the three mechanisms of horizontal gene transmission?
Transformation, Transduction and Conjugation
Explain each of the three mechanisms of horizontal gene transmission.
Transformation β the uptake of naked DNA from the environment Transduction β bacteriophages infect a bacterium and take up some of the bacterial DNA. The bacteriophage then carries the bacterial DNA to another bacterium. Conjugation β transfer of genetic material in the form of a plasmid via a conjugation tube
What is a Pathogenicity Island?
Horizontally acquired genes that contribute to the virulence
Why are cultures performed?
- confirm a dx - exclude a dx - screening - monitor the course of a disease - monitor response to therapy - stage the severity of the disease - provide a prognosis
How can results of a culture be altered?
- Collection methods: swab, aspirate, expectorant - physiologic variables transient bacteremia - meds: especially abx
General culture interpretation guidelines
- as a general rule: infection considered if >10^5 organisms found -
How long does it take cultures to grow?
1 full day to grow the organism and then part or all of 1 day to ID it. It may take an add. day to isolate it b/f ID if there is a mix of organisms. - a preliminary report for most cultures may be issued in 24 hours
What is important to ID from the infectious organisms?
- normal flora from the infection - normal flora and pathogens vary dependent on anatomic location
What is normal flora on the skin?
staph epiermidis, S. aureus, micrococcus, few gram - bacilli moist skin, corynebacterium, propionibacterium acnes
Pathogenic organisms on the skin?
strep. pyogenes pseudomonas proteus
Pathogens in the mouth?
strep pneumoniae, strep pyogenes, Neisseria meningitidis, H. influenza, N. gonorrheae
Potential pathogens and pathogens of oropharynx?
potentials: mycoplasma, bordatella pertussis, many others pathogens: staph aureus, pseudomonas
normal flora in conjunctiva?
corynebacterium, Neisseria, moraxellae, staph, strep, occasional Haemophilus and parainfluenza
Pathogens of the conjunctiva?
pneumococcus, pseudomonas, strep
pathogens of the GI tract?
C. diff, salmonella, toxic strains of E. coli, Helicobactor pylori (in duodenum)
Pathogens of anterior urthera?
chlamydia, gonorrhea, syphilis
What does the normal flora of the vagina depend on?
- varies with hormonal state
Pathogens of the vagina?
candida, trichomonas
What are important steps to collecting a specimen and achieving the highest diagnostic yield?
- obtain specimen before abx - use strict aseptic technique - minimize contamination by skin and mucous membranes (be careful with swabbing) - collect an adequate volume and send tissue or fluid rather then a swab when possible (culture when possible) - label appropriately - fill out requisition slips completely and precisely - call microbio dept if you have any ???s
within how many hours of collection should samples arrive in the lab?
within 1-2 hours of collection, but if delay is unavoidable most specimens (except blood, CSF
Culture turnaround times?
blood cultures: 48-96 hours most routine cultures (urine, throat, sputum): 24-48 hrs unless looking for unusual bacteria - anaerobes: can take 48-72 hours * almost always get gram stain with culture in most settings
appropriate culture media?
-routine: blood agar -chocolate agar -> gram negatives (GC & Haemophilus) -anaerobic blood agar: needs to be fresh -sabourad agar: fungi - GPS -> gram + selective media -> allows isolation of strep and staph and inhibits most gram - rods - MacConkey or eosin methylene blue agars: anaerobic gram - rods - Thioglycollate media: liquid media, enrichment broth used as supplement to plated media
Process of wound culture?
- usually pus present - round up some pus on an applicator - culture of specimens from the skin edge is less accurate than culturing the suppurative material - if anaerobic organism suspected -> get anaerobic culturette from lab
Culture of abscess/boil/furuncle
- incised and any fluid or material swabbed with culture swab and sent to lab - important to get pus/exudate from deep in the wound to avoid surface contamination
Culture of the eye-> conjunctiva
- gently swab to collect drainage - place in approp. container and send to lab at 25 degrees C
How to obtain throat cultures? when are these done?
- done to rule out strep pharyngitis (GABS) - sore throat, inflamed tonsils - inform lab if trying to ID something else such as N. gonorrheae (this reqrs Thayer-Martin agar) - swab posterior pharynx and tonsils - avoid touching any other part of mouth - send to lab at 25 degrees C - often indicated if the in office rapid strep screen is negative
Sputum culture indications
-HAP - hosp patients with pneumonia (CAP) and any of the following criteria: -ICU admission - failure of output abx therapy - cavitary lesion - active alcohol use (aspiration pneumonia) - severe obstructive of structural lung disease - + urine antigen test for pneumococcus - + urine antigen test for Legionella - pleural effusion
Sputum cultures are not indicated when:
- for most outpatient CAPs - management of bronchitis - initial management of acute exacerbations of COPD
How to obtain a sputum collection for optimal yield?
- obtain prior to abx tx - have the pt rinse their mouth prior to expectoration - no food 1-2 hours prior to expectoration - inoculation of culture media immediately after specimen is obtained or immediately after prompt transport to microbio lab - bronchoscopy: sampling of lower airway is another potential dx method in patients w/ suspected pneumonia
What may make a sputum culture inaccurate? When would you suspect a pathogen? When is the best time to get a sputum culture?
- may be inaccurate due to mouth flora - suspect a pathogen if WBCs are present along with an overabundance pf 1 type of organism -first morning sputum will represent deeper pulmonary secretions - induce cough with nebs, pulmonary PT, aspiration, bronchoscopy
What should you always get with a sputum sample?
- always get a gram stain too! - helpful for directing empiric therapy
What will you see in a atypical pneumonia sputum culture (mycoplasma and legionella)?
The sputum will contain abundant PMNs and few or no organism will be seen on the gram stain
What will you see on a sputum culture + with pneumococcal pneumonia?
abundant inflammatory cells and gram + diplococci
What are the indications for ordering a blood culture?
- bacteremia - septicemia - unexplained post operative shock - unexplained fever of several days duration - pneumonia - chills and fever in pts with: infected burns or UTIs rapidly progressing tissue infections post-op wound sepsis indwelling venous or arterial catheters -debilitated pts receiving: abx, corticosteroids, immunosuppressives, parenteral hyperalimentation (nutrition)
When are blood cultures used to detect bacteremia (septicemia)
- should mainly be considered in pts w/ temp >101 suspected of having endocarditis or other systemic pathogens - std of care for inpatients w/ pneumonia prior to starting abx - can repeat in 1 hour or if fever (transient bacteremia) - 2 specimens obtained from 2 separate sites 15 minutes apart (aerobic or anaerobic?) - # of organisms / site is low - helps id contaminants - total: 30-40 ml of blood
Blood culture technique
- clean site first with 70% alcohol - follow with butadiene x 2 minutes - wipe bottle tops with alcohol - go to lab immediately - donβt draw blood cultures through central lines or IV (contamination)
How to collect a urine sample?
- clean catch, mid void specimen - collect 5-50 ml of urine - cath -suprapubic tap *best culture is in the morning (most concentrated)
Guideline of urine sample and transport
- midstream clean catch urine by pt - need at least 1 ml - transport a 4 degrees centigrade - straight cath specimen: same parameters - indwelling cath: disinfect port with alcohol remove 5-10 ml of urine w/ needle and syringe -> transfer to sterile container, 4 C - suprapubic aspirate: at least 1 ml, at 4 C - always send as UA and urine C & S
What does the urine dipstick test?
- pH - specific gravity - bilirubin - protein (nephritis -> elderly) - glucose -> diabetics - ketones (diabetic ketoacidosis) - blood: canβt always rely on - nitrate: certain bacteria - leukocyte esterase (pyuria)
indicators of possible pyuria
leukocyte esterase: if + on dipstick likely indicates pyuria nitrite: indicates the presence of enterobacteriaceae that converts nitrate to nitrite if neg but + symptoms of UTI still want urine culture
Microscopic analysis of urine
- eval of urine sediment from a spun sample - presence of squamous epithelial cells = contamination from genital region - normals: rbc: 0-5 HPF wbc: 0-5 HPF bacteria: absent casts: 0-4 hyaline LPF (kidney health) crystals
Indications for a lumbar puncture
- look for blood (possible subarachnoid hemorrhage) - find the organism causing the meningitis or brain abscess - can do gram stain early on while awaiting culture reports - cell and chemistry counts will aid in making the dx
CSF Culture
- suspected meningitis, high fever in infant - lumbar puncture collect 1-5 ml of CSF - transport at 25 degrees C - gram stain and bacterial culture - 4 tubes for: cell count, glucose and protein, gram stain and culture, and cell count to compare to tube 1
Pleural fluid culture
- thoracentesis - dx and/or therapeutic: therapeutic- relieves dyspnea (breathe easier) diagnostic: test the fluid for TB, CEA level (tumor marker), cytology, culture, gram stain, pH
Go under or over rib while doing a thoracentesis?
- over because nerves and vasculature along bottom of ribs
Synovial fluid eval?
- swollen joint - infection, inflammation or uric acid -meds shouldnβt be administered therapeutically at the same time because interfere with sample (corticosteroids, abx)
Body fluids collection technique
- peritoneal, pericardial, pleural, synovial - aspirate using sterile technique into sterile syringe (usually pt has fever or elevated WBCs) - remove needle and cap syringe to send to lab, sometimes put aspirate in a different container - min. of 1-10 cc, send as much fluid as possible - send at 4 degrees C
Genital tract culture for women
- swab cervix for gonorrhea, chlamydia as well as other organisms in suspected PID - swabs of urethra or urine testing for chlamydia - occasionally swabs of vagina are done
guidelines for vaginal/cervical culture
- no douching or tub bathing for 24 hours prior to collection - swab -> checking for gonorrhea, chlamydia
When is a wet mount used?
- helpful in evaluating vaginitis - saline wet mount of vaginal discharge can show epithelial cells covered with bacteria suggestive of bacterial vaginosis - trichomonads - can reveal multiple PMNβs - KOH (K+ hydroxide) wet mount can reveal candida organisms
Swabbing male urethra indications
- special smaller swabs for urethral sampling for gonorrhea and chlamydia and other less common infectious agents - urine samples for GC and chlamydia for nucleic acid amplification - nucleic acid amplification more sensitive than culture
Urethral culture techniques
- usually on men - culture for GC, chlamydia - rapid enzyme test available - Thayer martin/New York media - anaerobic transport
Stool culture indications
- routine culture (for those with prolonged diarrhea or havenβt been on abx or hospitalized) - >2 grams, 4 degrees C - C. diff toxin: test of choice for those who develop diarrhea on abx or in hospital > 3 days - >5 ml, 4 degrees C
Stool culture guidelines
- also check for ova & parasites - usually look for staph, salmonella, shigella - Donβt mix urine or TP with sample - rectal swabs: worms - βtape testβ
Difference b/t acute and chronic cough?
- acute cough: only exists for less than 3 weeks and is most commonly due to an acute respiratory tract infection. Other considerations include and acute exacerbation of underlying chronic pulmonary disease, pneumonia, and PE - Chronic: cough that has been present longer than 3 weeks is either subacute (3-8 weeks) or chronic (more than 8 weeks)
Common causes of chronic cough
- post nasal drip from allergies or chronic sinusitis - asthma - postinfectious - chronic bronchitis - GE reflux - heart failure - medication induced (ACE inhibitors) - enviro irritants -> pollution
Mycobacteria infections
- Mycobacterium TB - Mycobacterium Leprae - Atypical & nontubercular mycobacterium
Definition of TB
- an infectious disease caused by the tubercle bacillus, Mycobacterium tb, and characterized pathologically by inflammatory infiltrations, formation of tubercles, caseation, necrosis, abscesses, fibrosis and calcification - most commonly affects the respiratory system
What type of stain do you use to dx TB
- Acid fast bacilli stain mycelia acid which makes up the wall of mycobacterium take up acid fast stain (wonβt show up in gram - or + stains)
TB epidemiology
- TB is one of worldβs deadliest disease: 1/3 of worldβs pop is infected with TB - each year over 9 mill people around the world are afflicted with TB - each year, almost 2 mill TB related deaths worldwide - TB is leading killer of individuals who have HIV -Incidences of TB in the U.S> has been decreasing. Increase in 1992 (18% increase compared to 1985) associated with HIV
Is the rate of TB declining in the U.S.?
- yes, the TB rate has been going down in U.S. each year since 1992 - the average annual % decline in the TB rate slowed from 6.6% for 1993 through 2002, to an avg decline of 3.4% for 2003 - 2008 - rate from 2013: 3.2%
Who accounts for most of the increase of TB cases?
- HIV patients account for 30-50% of increase - HIV is the greatest known RF for reactivating latent TB infection
Where has TB become prevalent?
- prevalent in populations co-infected with HIV and M. tuberculosis, such as inner city minority and injection drug users - in some inner city tb clinics: 40% of all pts with TB are infected with HIV - TB in foreign born individuals accounted for 53% of cases in 2004 (mexico, philippines, Vietnam, India and China)
4 possible outcomes of TB infection
- immediate clearance of the organism 2. chronic or latent infection (gets past initial immunity barriers into lungs) 3. Rapidly progressive disease (primary disease -> rapidly spreads throughout lungs, may spread to other organs) 4. Active disease many years after the infection (reactivation disease) may lay dormant for many years
Chronic (latent) infection
- person comes in with positive PPD but is asymptomatic with clear CXR - Person is infected but not infectious
Primary disease
- small bacilli carried in droplets small enough to reach alveolar space 2. If host system fails in clearing: - Bacilli proliferate inside alveolar macrophages and kill the cells - infected macrophages produce cytokines and chemokines that attract other phagocytic cells, including monocytes, other alveolar macrophages, and neutrophils, which eventually form a nodular granulomatous structure called the tubercle or Gohn focus - if the bacterial replication isnβt controlled, the tubercle enlarges and the bacilli enter the local draining lymph nodes, this leads to lymphadenopathy, a characteristic manifestation of primary TB - Caseation/fibrosis/calcification: ghon complex (caseation: necrosis of cells (look like cheese in middle of complex) - calcification is imp step in containing bacterium
steps of Primary disease infection
- bacilli reach alveolar space 2. proliferation inside macrophages 3. initial inflammatory granulomatous tubercle formation (if bacterial replication is controlled here, pt will not develop primary disease and is said to have chronic or latent infection) 4. Enlargement of tubercle and infiltration of lymph system (Gohn complex: describes an inflammatory nodule in the pulmonary parenchyma (Gohn focus) with an accompanying hilar adenopathy, in line with lymphatic drainage from the pulmonary segment
Symptomatic primary disease
- those who develop active disease w/in 2-3 years after infection - sever illness: lung necrosis, and extrapulmonary involvement
Main symptoms of pulmonary TB?
Central: appetite loss, and fatigue lungs: chest pain, coughing up blood, productive and prolonged cough Skin: night sweats, pallor (anemia from chronic disease)
steps of secondary/reactivation TB
- asymptomatic primary infection occurs 2. cell-mediated immunity: has contained the infection (neutrophils, macrophages -> gohn complex probably present) 3. dormancy 4. then, recurrence may occur
When does secondary/reactivation disease occur and what is it associated with?
- results when the persistent bacteria in a host suddenly proliferate (no longer contained b/c decreased immunity) - clearly assoc. with immunosuppression and can be seen in the following circumstances: HIV infection and AIDs end stage renal disease diabetes mellitus malignant lymphoma corticosteroid use * in contrast to primary disease: the disease process in reactivation TB tends to be localized, there is little regional lymph node involvement and the lesion typically occurs at the lung apices (where gohn lesion resided)
Signs and symptoms of secondary/reactivation of TB
cough, hemoptysis persistent fever/night sweats wt loss malaise adenopathy pleuritic chest pain
What is a Rasmussen aneurysm in TB?
- develops aneurysm and it ruptures
What is Miliary TB?
- if the bacterial growth continues to remain unchecked, the bacilli may spread hematogenously to produce disseminated TB - lung looks like it is covered with millet seeds -Miliary TB is used to denote all forms of progressive, widely disseminated hematogenous TB even if the classical pathologic or radiologic findings are absent
Acute and Chronic Miliary TB
Acute (primary infection) - high fevers, night sweats, Occ. Resp. distress, septic shock, multigrain failure - acute tend to be young Chronic: reactivation TB - fever, anorexia, wt loss, particularly in the elderly (FTT)
Extrapulmonary manifestations
- frequency is increasing - past hx is unreliable - 50% have normal chest radiographic findings - clinical features vary widely - most common type is infection of an individual organ system (bowel, bone, spleen, brain -> depends on where disease is expressed in the body) -in most cases, same regimens used for pulmonary TB are used systems that can be effected: - pleural/pericardial effusions (can lead to pericardial constriction) - lymph node infection: tuberculous lymphadenitis -> scrofula, seen in younger pts - kidney - skeletal: 35% -> potts disease - joints - CNS tuberculosis: meningitis, intracranial tuberculoma (mass lesion on the brain), spinal tuberclous arachnoiditis (similar to meningitis, arachnoid specific) intraabdominal TB: GI tract, peritoneum, renal TB, testicular granuloma - TB retinitis - muscles: (ex: psoas)
Dx of TB
dx in most cases are clinical - most persons dx w/ TB are begun on specific tx before dx is confirmed by the laboratory because it takes a long time to confirm dx - Around 15-20% of pts that are given a presumptive TB dx never have bacteriologic confirmation of disease
What can you say if person has positive PPD (mantoux)?
- has had exposure to TB infection
What kind of technique is used to examine sputum for TB?
- Ziehl neelsen test - takes a long time to culture mycobacterium
TB skin test?
- generally used as screening test, most sensitive test for dx of infection with mycobacterium TB - far more sensitive than a chest radiography - + TB skin test doesnβt by itself prove the presence of active disease but does indicate that infection has occurred - negative reactions have been doc. in 20% of pts who have TB - Primary use in detection of Latent TB infection - testing is targeted in persons at high risk for developing symptomatic TB who would benefit by tx of LTBI or those pts at increased risk for primary TB should they acquire infection - test is discouraged in those at low risk
Importance of TB skin test technique?
- must be done intradermally ( b/c confined area: protein derivative where T cells can get to) - Must form a visible wheal with injection (subcutaneous admin. will result in a false-neg. test if the pt indeed has been infected by TB)
How to read the TB skin test properly?
- must be read 48-72 hours (reaction is from delayed type hypersensitivity response mediated by T lymphocytes) - test is read by the diameter of the induration, not the diameter of the erythema - finger vs ballpoint pen method
Indicaions for TB skin testing?
- HIV infection - ongoing close contact with cases of active TB: health care workers prison guards mycobacterial lab personnel Presence of medical condition that increases risk of active TB: DM, steroid therapy, other immunosuppressive agents, certain types of malignancies, end stage renal disease, alcoholism, suppressed immune systems - medically underserved, low income population: homeless, injection drug users - residence in long term care facility: nursing homes, correctional institutions, mental institutions - single potential exposure to TB ( dx of TB of family member): repeat testing in 6-12 weeks if pt tested shortly after exposure - presence of incidentally discovered fibrotic lung lesion - immigrants and refugees from countries with high prevalence of TB
Sources of false-negative tests
- inadequate nutrition - anergy - nontubercular mycobacterium (bovus and avian) - simultaneous presence of immunosuppressive disorder - concurrent viral infection - corticosteroid therapy
Who would be considered for + TB skin test with induration > 5 mm
- HIV positive persons - recent contacts of TB case - fibrotic changes on chest radiograph consistent with old TB - pts with organ transplants and other immunosuppressed pts ( receiving >15 mg/d prednisone for > 1 month)
Who would be considered + for TB test with induration > 10 mm
- recent arrivals (10 %, gastrectomy, jejunolieal bypass - children
Who is considered + for TB with >15 mm induration?
- persons with no RFs for TB
+ TB skin test w/ BCG vaccine?
- children who received this vaccine generally demonstrate PPD reactions of 3-19 mm several months after vaccination - TB skin testing is not CI in BCG vaccinated persons: baseline testing should be done several months following vaccination - subsequent tests can be compared to baseline tests to eval. likelihood of true TB infection - responses indicative of new TB infection include: - increase in skin test reactivity > 10 mm induration in persons less than 35 yo - increases in reactivity of > 15 mm induration in persons greater than 35 yo * if baseline values unavailable: reactivity should be interpreted and tx as for unvaccinated persons
When should the sputum be evaluated?
- when active disease is suspected, there should be an exam of sputum for Acid Fast Bacilli staining and mycobacterium culturing - if pt unable to produce sputum spontaneously attempts should be made to induce sputum: hydration pulmonary physiotherapy mucolytic agents bronchoscopy or bronchoalveolar lavage * impt test: gold standard dx test: culture bacilli
Acid Fast Bacilli staining
- Mycobacterium have a cell envelope, unlike gram - bacteria, there is no true outer membrane in mycobacterium, the envelope is composed of a number of different macromolecules including mycolic acid - AFB smear: makes presumptive dx of TB in high risk pt - not specific for Mycobacterium TB (other acid-fast organisms will be positive such as mycobacterium avium and bonus) - 2 versions: fluorchrome staining: decreases exam time and increases sensitivity versus Ziehl-Neelsen method but is expensive Ziehl Neelsen method (older)
Mycobacterium culturing
- gold std of dx of TB - slow growth rate Solid media: lowenstein- Jensen or Middlebrook - takes up to 8 weeks or longer to detect growth Liquid media: expensive, broth formulations, more rapid and can detect growth of mycobacteria in clinical samples in as few as seven days
Other screening test for TB
- whole blood interferon gamma assay (Quantiferon-TB Gold test) - screening test for asymptomatic disease - T cells of individuals previously sensitized with TB AGs will produce interferon gamma when they reencounter mycobacterial AGs - 99% accurate reading - can be used in all circumstances in which PPD is used (have negative PPD and have been exposed)
Advantages of Quantiferon-TB gold test over skin test?
- subject to less testing error - subject to less reader bias and error - can be accomplished after a single pt visit - may not be as likely to be positive following BCG vaccination - The RD1 AGs used in this testing are not shared with most nontuberculous mycobacteria (bonus and avium)
Rapid nucleic acid assays?
-Can produce results within 2-7 hours after sputum processing - requires higher level labs - highly specific for Mycobacterium TB and is generally recommended on all AFB smear-positive respiratory specimens - + nucleic acid assay of AFB smear positive respiratory sample is dx of TB
Characteristics of mycobacterium
- rod shaped bacteria with lipid rich cell walls - they grow very slowly and take a long time to eradicate with antibacterials
TB management for latent infection
- 9 months of Isoniazid alt: Rifampin PO daily for 4 months
Tb management for reactivation TB disease
- requires at least 2 effective drugs b/c of increased incidence of drug resistance - Initial therapy of active TB include 4 drugs: - INH - RIF - Pyrazinamide (PZA) -Ehtambutol (EMB)
MOA of INH
- covalently binds to and inhibits enzymes essential for synthesis of mycolic acid * very specific to TB b/c of mycelia acid cell envelope - never used alone as resistant organisms will rapidly emerge AEs: hepatotoxicity: monitor liver enzymes - most common SE: peripheral neuritis which manifests as paresthesias and is assoc. with pyridoxine ( Vit B6) deficiency
MOA of Rifampin
- broader antimicrobial activity than INH - blocks transcription by interfering with the beta subunit of bacterial RNA polymerase - in add. to mycobacteria -> effective against many gram + and - bacteria (frequently used prophylactically for individuals exposed to meningitis caused by meningococci or H. influenzae - AEs: hepatotoxicity, liver enzymes inducer of cytochrome P450 enzymes and therefore the pt may need higher dosage requirements for other drugs metabolized by this system
MOA of Pyrazinamide
- unknown - only seen in anti tubercular combo packages - AE: extensively metabolized by liver, must watch for hepatotoxicity - gout
MOA of ethambutol (EMB)
- inhibits an enzyme important for the synthesis of the mycobacterial arabinogalactan cell wall - AEs: optic neuritis: results in diminished visual acuity and loss of ability to discriminate from red and green - eye exams regularly (every couple of weeks)
Alt. second line drugs for TB
- aminsalicylic acid - capreomycin - cylcoserine - ethionamide - fluoroquinolones* - macrolides* (used outside of TB tx)
Resistance to TB drugs
- multi drug resistance: Isoniazid and Rifampin Extremely drug resistance: use Isoniazid, Rifampin, a fluoroquinolone, and injectable (amino glycoside) - requires ID specialist - 18-24 months tx - surgery often required
Why are there pt compliance issues?
- b/c sxs are often gone w/in 2 months of initiating multi drug therapy yet the pt must continue therapy for 6 months - 2 years before organism is fully eradicated - TB occurs with a higher incidence in several pt populations that show higher noncompliance (injection drug users) -
What can help with compliance issues?
DOT therapy: directly observed therapy - trained health care worker or other designated individual (excluding family member) provides the prescribed TB drugs and watches pt swallow every dose - nurse or supervised outreach worker from county public health dept can provide DOT
Chemistry of bactericidal cell wall inhibitors?
Penicillins, cephalosporins, monolactams, and carbapenems all have b-lactam ring in the center. Some of these are inactivated if the ring is cleaved by B-lactamases. monolactams and carbapenems are are reisistant to B-lactamases
What is used with penicillins and cephalosporins to inhibit b-lactamases?
Clavulanic acid binds and inhibits B-lactamase. - augmentin is trade name for amoxicillin and clavulanic acid. - Timentin is trade name for ticarcillin and clavulanic acid.
What results in higher serum levels of penicillin?
probenicid, it acts by competing with penicillin for the organic anion transport system which is primary route of penicillin excretion β> results in higher levels of penicillin in the serum.
Mechanism of Penicillin G?
B-lactam binds PBPs and inhibits cross linking of bacterial cell wall components
