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Divisons of dna viruses
Single stranded vs double stranded and enveloped vs non enveloped
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Double Stranded enveloped DNA viruses
- Herpes simplex virus type 1
- Herpes simples virus type 2
- Varicella Zoster virus
- epstein barr virus
- cytomegalovirus
- Hepatitis B
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Divison of RNA virus
- Single vs double stranded
- For singled stranded positive vs. negative
- Non-enveloped vs enveloped
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Aerobic Gram + cocci coagulase + custers
staphylococcus aureus
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Aerobic Gram + coagulase - clusters
Staphylococcus epidermidis and staphylococcus saprophyticus
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Aerobic gram + cocci in pairs
- Enterococcus spp., alpha hemolytic strptococci,
- and beta Hemolytic streptococci
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Aerobic gram-positive bacilli
- Bacillus spp.
- coynebacterium spp.,
- gardnerella barinalis,
- actinomyces spp.,
- lactovavacillus acidophilus,
- listeria monocytogenes,
- nocardia spp.
- rhodococcus equi
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Aerobic gram - bacilli
enterocacteriaceae
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Aerobic gram - bacilli Coliforms
- Escherichia coli
- Klebsiella spp.
- Enterobacter spp.
- Serratia marcescens
- Citrobacter spp.
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Aerobic gram - bacilli Non-coliform
- Proteus spp.
- Providencia stuartii
- mroganella morganii
- Salmonella spp.
- Shigella spp.
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Aerobic gram - fermentors
- Enterobacteriaceae
- aeromonas hyprophila
- Vibrio Cholerae
- Pasterella multocida
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Aerobic gram - Non-fermentors
- Pseudomonas aeruginosa
- Acinetobacter spp.
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Gram _ fastidious
- Haemophilus spp
- campylobacter jejuni
- Legionella pneumophilia
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Aerobic gram - cocci
- Moraxella catarrhalis
- Neisseria spp.
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Gram + anerobes
- Clostridium spp.
- peptostreptococcus spp.
- Propionibacterium acnes
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Anaerobes Gram -
- Bacteroides fragilis
- Prevotella spp.
- Fusobacterium spp.
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Atypical Bacteria
- Chlamydia spp.
- Mycoplasma spp.
- Legionella spp.
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Minimum Inhibitory concentration (MIC)
the lowest concentration of an agent that inhibits the visible growth of an organism
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Minimum bactericidal Concentration (MBC)
The lowest concentration of an agent that results in a 99.9% reduction in colony forming units.
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Methods for determining MIC
- Macro-broth dilution
- micro-broth dilution
- agar dilution
- kirby bauer disk diffusion
- Epsilometer strip
- automated system
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Breakpoint values
- system developed to aid clinicians evaluate MIC results.
- Breakpoint value is based on:
- drug pharmacokinetics and pharmacodynamics
- distribution of MICS of a population of bacteria
- clinical efficacy
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Antibiogram
summarize of bacteria suscepatibleity to antibiotics
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Limitations of MIC
- Do not provide regarding the rate or extent of bactericidal activity
- MIC are conducted with a standard incoulum
- Media does not contain plasma proteins or complement
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Serum inhibitory and bactericidal titers-schilcter test
Following a dose blood is obtained and serially diluted. Bacteria are added to the serum and the inhibitory and bactericidal titers recorded.
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Serum inhibitory titer (SIT)
the largest dilution of a sample that inhibits the visible growth of an organism
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Serum bactericidal titer (SBT)
the largest dilution of a sample that results in a 99.9% reduction in colony forming units.
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Interpretation of SIT and SBT
- Larger dilutions contain less drug
- SIT and SBT take individual pharmcokinetics into account
- Can be used to evaluate antimicrobial therapy
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Time kill curves
- provide data regarding the dynamics of antimicrobial activity
- broth is inoculated with a test isolate at a standard inocula and a known amount of antibiotic
- Samples are removed from testing containers at predetermined time points and plated on agar
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Inappropriate antibiotic use by clinicians
- overuse of broad-spectrum agents
- used for the treatment of non-bacterial infections
- inappropriate antimicrobial prophylaxis
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Lack of patient education or ineffective education
- Failure to complete antimicrobial regimens
- non-compliance
- patient self-medication
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Widespread antimicrobial use in the food production industry
- Nearly 1/2 of the antibiotic usage is in farm animals
- increasing reliance on aquaculture
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Primary Resistance
- Naturally occurring
- Prior antimicrobial exposure is not required
- predictable
- also refereed to as inherent, intrinsic , or native resistance
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Secondary resistance
- develops following antimicrobial exposure
- Not predictable
- Also referred to as acquired resistance
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selection of resistant subpopulation
- a bacterial population is comprised of isolated with varying MIC
- Isolates with low MIC are easily killed
- Resistant subpopulations remian grow
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Genetic alterations
- Spontaneous mutiations
- acquisition of new genetic material
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Strategies to precent the spread of antibiotic resistance
- Patient education
- knowledge of local susceptibility patterns
- prescriber education
- develop guidelines for appropriate antimicrobial usage
- vaccination
- Hand washing
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Positive Stand RNA virus enveloped
- rubella
- west nile
- Hepatitis C
- HIV
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Negative stand enveloped RNA virus
- Influenza virus
- Respiratory syncytial virus (RSV)
- Mumps
- measles
- rabies
- ebola
- haunta
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Genome
- Either DNA or RNA-NOT BOTH
- Single stranded ss or double stranded DS
- sommonly ds DNA or ss Rna
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SS RNA
the positive stand can be used directly as a template for protein synthesis while the negative strand cannot.
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Capsid
- Protein shell
- helical-rod shaped or coiled
- icosahedral-symmetrical
- complex-not helical or icosaherdral
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Steps of viral replication
- 1. Viral adsorption/attachment
- 2. viral penetration
- 3. Viral uncoating
- 4. replication of the viral genomes and other viral components
- 5. self-assembly of progeny viruses (viral replication)
- 6. Release of progeny viruses
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Viral adsoprtion/attachment
- attachment of virus to a host cell
- viral attachment structures
- cell surface proteins often hijacked by viruses
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Viral pentration
passage of the complete virus from the target cell surface into the cytoplasm through the membrane
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Viral uncoating
- disassembly of the complete virus
- depend on enzymes from the infected cells
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abortive infection of the host cells
- No progeny virus is produced
- the virus enters a cell that lack necessary machineries for replication
- a defective virus
- Cell death due to viral infection
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Latent infection of host cells
viral genome is within the infected cell, but no progeny is produced until viral reactivation
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Persistent activation
The infected host cell lives and continues to divide and function
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Lytic infection
the infected host cell dies because its normal macromolecule metabolism is impaired the infecting virus aims to maximize viral replication.
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Fall-Spring seasonal viruses
- Influenza A & B
- Respiratory synacial virus
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Fall, spring
Parainfluenza 1,3,4
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Spring Fall seasonal virus
- West Nile Virus
- enterovirus
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Winter Seasonal Virus
Rotavirus
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All season virus
- Parainfluenza 3
- Noravirus
- Adenovirus
- Herpes Simplex
- Varicella zoster
- Cytomeglovirus
- HIV
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Herpesviridae
- Replicate within the nucleus
- The envelop contains antigenix glycoproteins that are species and tissue specific
- Following primary infection, all herpes virus can enter into the latent phase and be activated at a later time throughout life
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Alphaherpesvirinae
- Herpes simplex virus 1
- Herpes Simplex Virus 2
- Varicella Zoster Virus HHV-3
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Betaherpesvirinae
- Cytomegalovirus HHV-5
- Human herpes virus 6
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Gammaherpesvirinae
- Epstein Barr Virus HHV4
- Human herpes virus 8
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Common site of HHV 1
oropharyngeal and labiofacial surfaces, other sites
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Common Site of HHV 2
Genital squamous surfaces
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Transmission of HHV 1
- Saliva to oropharyngeal and labiofacial surfaces
- Some cases of skin-to-skin transmission
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Transmission of HHV 2
Intimate sexual contact
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Presentation of HHV1 and HHV 2
cutaneous herpes lesions that heal without scarring
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Latency of HHV 1
Migrate through the sensory nerves fibers to the trigemental gangion and persists indefinitely in a dormant state
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Latency of HHV2
- Migrate to the sacral neural ganglia.
- Reactivation rates are at least twice as high with HHV 1
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Immunocompromised Patients and HHV
- Reactivate of HHV is only a problem for immunocompromised patients
- Encephalitis and meningits are the main problems
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Varicella Zoster Virus-Chicken pox
- Prutic vesicles progresses to ulcers, crust over and heal without scarring
- mild symptoms and minimal sequalae
- Virons travel by nerve fivers to regional sensory neural ganglions
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Varicella Zoster virus-Shingles
- Reactivation of primary infection
- Spreads from trigeminal or dorsal root ganglia back down nerve fibers to the skin producing painful cutaneous vesicles with a classic dermatome distribution
- Can be very painful
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Human papillomavirus (HPV)
- ds non-enveloped DNA virus
- over 70+ strands
- Induce hyperplastic epithelial lesion and malinancies
- Most HPV warts of the hands and feet are transient and has no medical consequence
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sexually transmitted HPV
- Anogenital wart: HPV 6 HPV 11
- Carcinoma: HPV 16 HPV 18
- Oral Cancer: HPV 13 and HPV 32
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Human Herpes 8 virus
Kaposi sarcoma in severely immunocompromised patients. Specifically AIDs
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Exanthems
- Widespread rash usually in children
- Caused by viruses that spread hematogenously to skin and mucous membranes
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Coxasackie virus (hand-foot-and mouth disease)
- Transmitted by direct contact with nose and throat discharge, saliva, fluid from blisters, or the stools of an infected person
- most contagious during the first week; 3-7 days before system appear
- transmission by inhalation or ingestion
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Other Coxasackie viruses
- Herpangina
- myocarditis
- myostit
- pericarditis
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HHV 6 Roseola
- A high fever followed by a rash on neck trunk and thigh commonly seen in infants
- transmission from saliva possible
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Measles Virus
- ssRNA - enveloped viruses
- transmission by sneezing/coughing droptlets
- extremely infectious
- Replicate in respiratory epithelial cells, then in lymphoid organce
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symptoms of measles
- Rash
- fever
- upper respiratory tract symptoms
- conjuncitivitis
- Initial infection probably occurred 1-2 weeks prior
- Once the rash appears the patient is not infectious
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Rubella Virus
- ssRNA + enveloped viruses
- Respiratory transmitted
- Commonly called german measles
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Congenital rubella
significant damages to fetus due to necrosis in fetus
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Smallpox
- One of the most deadly viral infections in human history
- Large ds DNA virus with complex genome
- Caused by either of two virus variants
- variola major and minor
- No specific treatment the only prevention is vaccination
- potentials as biologic weapon
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Transmission of smallpox
- direct and fairly prolonged face-to-face contact
- direct contact with infected bodily fluids or contaminated objects such as bedding or clothing
- respiratory-uncommon
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Disease course of small pox
- Incubation 1-2 weeks, asymptomatic, not contagious
- Early symptoms, 3-4 days, high fever, malaise, head and body aches, and sometimes vomiting, may be contagious
- Rash and pustules, 1-2 weeks very contagious
- Resolution, 1 week contagious
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Parainfluenza 1-4
- common cold
- pneumonia
- croup in young children
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respiratory syncytial virus (RSV)
Lower respiratory tract infections
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Human metapneumorvirus
Upper and lower respiratory tract infections.
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SARS corona virus
- Severe acute respiratory syndrome
- Causes both upper and lower respiratory tract infections, muscle pain, fever
- Highly contagious; 10% mortality
- Originated from China & spread to N America
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Rotavirus-
- Around winter months
- Causes most cases of watery diarrhea in infants and young children in the US
- Highly infectious 30%-50%
- Dehydration with electrolyte imbalance is the most serious complication
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Adenovirus enteritits
Clinically similar to rotavirus disease but has no seasonality
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Norovirus
- affect children and adults-BUT NEVER INFANTS
- year round
- Can be non-enveloped can survive for days on inanimate surfaces
- acute gastroenteritis
- Oral fecal transmission
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Coronavirus and astrovirus
Cause nosocominal and day care center outbreaks
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Mumps
- ssRNA - enveloped viruses
- Transmission by respiratory droplets followed by viremia
- Usually affect children
- Acute febrile infection and swelling on the parotid gland in 2/3 patents
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Complications of Mumps
- Viral encephalitis
- Deafness
- Male sterillity
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HSV encephalitis
- Uncommon in immunocompetent patients
- Usually occurs as a reactivation of latent HSV-1 that tracks into the cerebral cortex, producing a large necrotic mass
- Progression is rapid and mortality is high
- We have drug therapy for this
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Enteroviruses
- ~75% of viral meningitis in the US
- usually a relatively benign and transient disease in children and young adults
- coxsacki virus and echovirus
- spread easily from person to person via fecal oral means
- Often with annual summer-fall outbreaks
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Polio Virus
- Very uncommon in the US
- transmission by ingestion
- necrosis of spinal cord or brainstem motor neurons
- Many asymptomatic but can cause flaccid paralysis
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Arbociruses
- This family mostly comes from insects
- Flavivirus
- togavirus
- bunyavirus
- West Nile virus
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West nile virus
- simple fever to meningits, encephalitis, and flaccid poliomyelitis paralysis
- Long term encephalitic and paralytic disabilities
- many fatalities-mostly elderly and immunocompromised patients
- Detected by IgM and IgG in CSF or serum
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Infectious Mononucleosis
- caused by Epstein Barr cirus
- spread by saliva and infect B cells
- primary infection in early childhood is usually asymptomatic
- Classical occurs in the young adult years
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Signs and symptoms of mononucleosis
- sore throat
- fever
- tonsillitis
- lymphadenopathy
- splenomegaly
- hepatitis
- fatigue
- malaise
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Other diseases Epstein barr virus
- Nasopharyngeal carcinoma in Asians
- Burkitts lymphoma Africa
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Chronic Fatigue Syndrome
- Defined by clinical signs and symptoms rather than laboratory results
- Presistent fatigue accompanied by:
- fever
- pharyngitis
- tender lymphadenopathy
- athralgia
- myalgia
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Epstein Barr Virus (EBV)
- Reactivation of latent EBV infection is linked to:
- B cell CNS Lymphoma in AIDS patients
- Post-transplant lympohoproliferative disorder (PTIF) in transplant patients
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Cytomegalovirus (CMV, HHV-5)
The most common opportunistic viral infection in HIV and transplant patients
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Cytomegalovirus symptoms
- Pneumonia
- Hepatitis
- encephalitis
- esophagitis
- enterocolitis
- gastritis in HIV/AIDS patients
- Retinitis
- GI tissue damage
- graft damage in transplant patients
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Polyoma viruses
JC virus and Bk virus
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Progressive multifocal leukoenocephalopathy (PML)
a rare fatal and demyelinating CNS disease
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Parovirus 819
Refractory anemia and pansytopenia(low WBC, RBC, and platelets)
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Rabies Virus ssRNA-
- transmission by direct animal/human bite sometimes by respiratory tract by infected bat dropping
- The virus replicate locally then move to the CNS through the peripheral neurons and then move to many organs through the autonomic nervous system
- Disease course 1-8 weeks latent in the beginning but highly variable
- Hallucinations, mental dysfunction, aggression, seizure, coma and death
- Once symptoms begin death is inevitable
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Ebola Virus
Hemorrhagic fever high mortality
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Marburg Virus
- Hemorrhagic fever
- high mortality
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Hanta virus
- Hemorrhagic fever with or without renal syndrome and pulmonary syndrome
- high mortality
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Beta lactamases
- Produced by numerous gram+ and gram- microorganisms
- Inactivate beta lactam antibiotics by splitting the amide bond of the beta lactam ring
- Production of beta lactamases is either constitutive or inducible
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Microorganism with inducible beta lactamases
- Enterobacter spp
- Citrobacter freundii
- Serratia marcescens
- Pseudomonas aeruginosa
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Several agents are potent inducers of beta lactamases
- Cefotaxime
- ceftriazidie
- imipenem
- Ceftazidime
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Extended spectrum beta lactamases (ESBL)
- Active against all B-lactams except cephamycins, cefepime, and carbapenems
- Inhibited by B-lactamase inhibitors
- Most commonly found in K. pneumonia and E. coli
- Genes are located on plasmids
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AmpC type B-lactamases
- Active against all B-lactams except cefepime and carbapenems
- not inhibited by b-lactamse inhibitors
- Most commonly found in K. pneumonia, enterobacter spp, C. freundii, M. morgannii, S. marcescens, and P. aeruginosa
- Genes found on chromosomes and plasmids. Expression may be inducable
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Klebsiella pneumoniae carbapenemase (KPC)
- Encoded for by the blaKPC gene
- Extensive cross resistance with other classes of antibiotics
- Only susceptible to colistin or tigecycline
- Expression is independently associated with increased mortality
- Standard susceptiblity testing may not identify KPC production
- Use a modified Hodge test
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Strategies to overcome B-lactamase mediated resistance
- Administer large doses of B-lactams to overwhelm the B-lactamases
- Combine b-lactams with b-lactamase inhibitors such as tazobactam, clavulanate, and sulbactam.
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Aminoglycoside resistance modifying enzymes
- Modification as the aminoglycoside is transported across the cell wall of the microorganism
- Commonly observed among enterococci exhibiting high lavel aminoglycoside resistance
- Chloramphenicol acetyltransferase
- erthromycin estrase
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Alteration of the antimicrobial target or active site
- 1. Penicillin-binding proteins (PBP)
- 2. ribosomal binding sites
- 3. Cell wall precursors
- 4. DNA gyrases
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Alterations in bacterial cellular membranes
- Porin channels-Change in #
- Transport proteins
- Effllux Pumps-proteins that actively pump agent out of the bacteria
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B-lactams Gram +
- Most resistance is secondary to expression of PBP that bind B-lactams with low affinity
- Staphylococcus are the only gram+ that produce B-lactamses
- staphylococci can also express an altered PBP2a.
- This is encoded for by the mec determinant found on the mobile staphylococcal chromosomal cassette mec elements
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Gram- B-Lactams
- Most reistance is seondary to the production of B-Lactamses
- developed in 4 waves:
- 1. emergence of narrow spectrum penicillinases
- 2. ESBL(resistance to extended spectrum cephalosporins, mainly K. pneumoniae
- 3. CTX-M
- 4.Carbapenemases
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Glycopeptides
- High level resistance results from expression of operons that substitute a terminal d-lactate or d-serine for d-alanine
- Reduced vancomycin affinity
- Typically is only stable in the setting of continued vancomycin selective pressure
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Fluoroquinolones
- Resistance reults secondary to accumulations of point mutations in topoisomerases
- In general single point mutations result in low-level resistance-Mutant prevention concentration
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Methicillin-resistant Staphylococcus aureus (MRSA)
- Common nosocomial pathogen
- Isolation in the community is increasingly common especially among IVDU
- Resitance is secondary to the production of an altered PVP
- Resistance may be transferred via plasmids or transposons
- Multiple resistance to many common anti-staphylococcal agents is frequently encountered
- Treatment of choice is vancomycin
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Vancomycin Intermediate susceptibility(VISA)
- VISA may be due to alterations in the cell wall and altered autolytic expression.
- TMP/SMX may be a treatment option for VISA
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vancomycin resistant susceptibility(VRSA)
VRSA isolates possessed mecA and vanA genes. This suggests transfer of resistance determinants from enterococci
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Penicillin resistant streptococcus pneumoniae
- S. pneumoniae is a common cause of a variety of community acquired infections including otits media, pneumonia, sinusitis, and pneumonia
- Overuse of antimicrobials in the community setting has overtime selected for resistant organisms
- The prevalence of penicillin-resistant isolates in the United states has risen
- The prevalence of penicllin resistance caries geographically and found more with people under the age of 6
- Pneumococcal resistance to penicillin is the result of expression of modified penicillin binding proteins
- Antimicrobial resistance in vitro does not necessarily translate into clincal resistance
- In the case of pneumonia even high level PCN resistance among pneumococci has not been clearly associated with PCN failure
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Enterococcus
- Increasingly common nosocomial pathogen
- Intrinsically resistant to numerous antimicrobials including cephalosporins and TMP/SMZ
- Monotherapy with penicillins or vancomycin are static
- Combination therapy with an aminoglycoside is necessary for a cidal effect
- acquired resistance to the penicillins is due to alterations is PBP
- High level aminoglycoside resistance is conferred by the production of amino glycoside modifying enzyems
- Isolation of vancomycin resistant strains is becoming increasingly problematic
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Three distinct genomic variants are responsible
- Van A: Inducible high level resistance to vancomycin and teicoplainin
- Van B: Inducible resistance to vancomycin susceptible to teicoplanin
- Van C: constitutive resistance to vancomycin may be susceptible to teicoplanin
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treatment strategies for enterococcus
- Vancomycin, linezolid, daptomycin. and streptogramins
- Intermittent vs. continusous infusions of b-lactams and vancomycin
- Tradition vs. once daily dosing of amino glycosides
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