(8): What is the appropriate dose? - The appropriate dose is determined by the integration of PK and PD properties and parameters, such as AUC/MIC, Time>MIC, and C max /MIC. - Considerations: Dosing interval, risk of side effects, potential for superinfection, cost of therapy (9): Will initial therapy need modification after culture data has returned? - Narrow vs Broad: Switch to narrow-spectrum agent to decrease risk of colonization and possible superinfection o à De-escalation - Susceptibility data: When available, switch to the appropriate cheapest and safest compound with efficacy o à Pathogen-directed therapy - Clinical Course: Before making a change, assess the patient’s clinical response, vitals, radiography, labs, and microbiological response. (10): What is the optimal duration of treatment, and could resistance occur during prolonged therapy? - The optimal duration of abx therapy is not well established. There are common recommendations for each type of infection but these have been relatively empiric. This must be individualized and based on how the patient is responding to therapy - Development of Resistance: After several days of therapy with a specific agent, the pathogen may become resistant to that agent. The setting in which this is most likely to occur is when b-lactam agents such as new- generation cephalosporins are used to treat Pseudomonas species and other nosocomial gram-(-) bacilli. - Prevention: Only the prudent use of abx and infection protection measures will limit or prevent the spread of abx resistance (1/26) Danziger Lecture: Medical Microbiology: Microbes – Invisible Invaders, Amazing Allies Microbiology: The study of disease conferred by organisms too small to be seen without magnifications. This includes: Bacteria, Viruses, Fungi, Protozoa, Helminths (worms), Prions, Algae. - But not all microbes cause disease. In fact, >90% of the cells in the human body are microbes, we have an intimate relationship. Only 1% of all known bacteria cause human disease, whereas 4% cause plant disease. - 95% of all known bacteria are non-pathogens. We live symbiotically, though a weakened immune system may be susceptible to bacteria formerly considered non-pathogenic. - Advancements in hygiene, water filtration, and public sanitations are the largest contributors to the decrease in infection mortality. Antibiotics are a significant player as well. Addressing an infection: If we get infected, chances are that the internal balance of microflora has changed, or the immune system is fried. Initially, treatment is empiric-based. This means we are guessing the identity of the infectious agent. How do we know? Understand the Environment: Each organ has its own natural microbiome. By knowing the common inhabitants of those organs, we can quickly identify what should and should not be present in our attempt to assign therapy. If a patient has an infection, we expect it to be one of our normal flora organisms, simply out of balance. Understand the Acquirement: Normal flora are derived from: - The maternal genital tract - The skin of attendants/patients/nurses - The mouth and pharynx of close contact. See –eng. ‘Snogging’ - Air-borne organisms - Environment + Food Know the Pathology: The normal flora are inhabitants of the surface. They are adapted to their local environment, and are harmless in their usual site. However, they can potentially become pathogenic when they enter tissues, such as by injury, surgery, etc.
Transcript
(8): What is the appropriate dose? - The appropriate dose is determined by the integration of PK and PD properties and parameters, such as
AUC/MIC, Time>MIC, and Cmax/MIC. - Considerations: Dosing interval, risk of side effects, potential for superinfection, cost of therapy
(9): Will initial therapy need modification after culture data has returned? - Narrow vs Broad: Switch to narrow-spectrum agent to decrease risk of colonization and possible superinfection
o à De-escalation - Susceptibility data: When available, switch to the appropriate cheapest and safest compound with efficacy
o à Pathogen-directed therapy - Clinical Course: Before making a change, assess the patient’s clinical response, vitals, radiography, labs, and
microbiological response. (10): What is the optimal duration of treatment, and could resistance occur during prolonged therapy?
- The optimal duration of abx therapy is not well established. There are common recommendations for each type of infection but these have been relatively empiric. This must be individualized and based on how the patient is responding to therapy
- Development of Resistance: After several days of therapy with a specific agent, the pathogen may become resistant to that agent. The setting in which this is most likely to occur is when b-lactam agents such as new-generation cephalosporins are used to treat Pseudomonas species and other nosocomial gram-(-) bacilli.
- Prevention: Only the prudent use of abx and infection protection measures will limit or prevent the spread of abx resistance
(1/26) Danziger Lecture: Medical Microbiology: Microbes – Invisible Invaders, Amazing Allies Microbiology: The study of disease conferred by organisms too small to be seen without magnifications. This includes: Bacteria, Viruses, Fungi, Protozoa, Helminths (worms), Prions, Algae.
- But not all microbes cause disease. In fact, >90% of the cells in the human body are microbes, we have an intimate relationship. Only 1% of all known bacteria cause human disease, whereas 4% cause plant disease.
- 95% of all known bacteria are non-pathogens. We live symbiotically, though a weakened immune system may be susceptible to bacteria formerly considered non-pathogenic.
- Advancements in hygiene, water filtration, and public sanitations are the largest contributors to the decrease in infection mortality. Antibiotics are a significant player as well.
Addressing an infection: If we get infected, chances are that the internal balance of microflora has changed, or the immune system is fried. Initially, treatment is empiric-based. This means we are guessing the identity of the infectious agent. How do we know? Understand the Environment: Each organ has its own natural microbiome. By knowing the common inhabitants of those organs, we can quickly identify what should and should not be present in our attempt to assign therapy. If a patient has an infection, we expect it to be one of our normal flora organisms, simply out of balance. Understand the Acquirement: Normal flora are derived from:
- The maternal genital tract - The skin of attendants/patients/nurses - The mouth and pharynx of close contact. See –eng. ‘Snogging’ - Air-borne organisms - Environment + Food
Know the Pathology: The normal flora are inhabitants of the surface. They are adapted to their local environment, and are harmless in their usual site. However, they can potentially become pathogenic when they enter tissues, such as by injury, surgery, etc.
Matching Infections to their Suspected Organisms: If infected in these locations, these are the likely pathogens! Pharyngitis: In general, the causative bacteria are Group A Streptococci Acute Sinusitis (URTI): Most commonly associated with: S. pneumoniae, H. influenza, M. catarrhalis Chronic Sinusitis: More work needs to be done with this location, but potentially Anaerobes Epiglottis: This should be regarded as a medical emergency. Infection and inflammation of the epiglottis can block the trachea, preventing aspiration. Likely pathogen: H. Infleunzae
- Otitis: Most commonly H. influenza, S. pneumoniae, M. Catarrhalis - Bronchitis: Most commonly: H. influenzae, S. pneumoniae, M. catarrhalis - Pneumonia: Most commonly: S. pneumoniae, H. influenzae, M. catarrhalis, M. tuberculosis,
viral, and Mycoplasma. - **The above 3 infections have significant overlap in the commonly suspected organisms. As
a result, we can likely cover all three sites with the same abx! How wonderful. This last one, however, is different - Hospital Acquired Pneumonia (HAP, VAP): HAP often has many resistant pathogens, such as S. aureus, and
other gram(-) bacteria displaying resistance. Endocarditis-Subacute: Infection of the heart valve most frequently associated with S. viridans Endocarditis-Acute (IVDA): Intravenous drug abuse, conferring S. aureus, gram(-) rods, Enterococcus Endocarditis-Acute (Prosthetic Valve): Often related to S. epidermis Osteomyelitis/Septic Arhtritis: Infection of the bone is almost always the gram(+) S. aureus. The gram(-) infections often occur secondary to bone injury/surgery
Meningitis: An infection of the CNS, the suspected organisms for this condition are highly variable and dependent on age group. This is a serious condition requiring immediate attention. In newborns, Group B Streptococcus and S. pneumonia are the greatest contributors. In infants and children, S. pneumoniae, N. meningitides, and H. Influenzae type b (Hib) are common
Urinary Tract Infections (Community): Outside the hospital, E. coli, K. pneumoniae, and S aureus Urinary Tract Infections (Hospital): Within the hospital, Enterococcus and resistant gram(-) rods Skin and Soft Tissue Infections: Gram(+) bacteria, staph and strep Intra-abdominal infections: B. Fragilis, E. coli, Enteroccus FYI: Your feces, your excrement, your shit… is 50% bacteria by weight. The more you know!
Anatomical Sterile Sites - By now you’re likely thinking we have bacteria crawling on us everywhere at all times. Wrong! We have sterile
sites. These are our normally sterile sites: CNS, Cardiovascular System, URT, Bones and Joints, Urinary Tract o If we find bacteria at any of these sites, they should be sterilized, killed. IMMEDIATE TX!
Host Defenses against Infection - The human species has evolved over time in an environment pervaded by bacteria. As such, so have our defenses: - Mechanisms: Tears (lysosomes), Mucus (barrier), defensins (in intestinal epithelium, controlling colonization),
Ciliated epithelium (moves bacteria out of URT and into digestive tract), Gastric acid (lethal), Microbial flora (competition), Intact Skin (Barrier)
- Koch’s method involves isolating microorganisms from a dead animal, culturing them, identifying them, injecting into a healthy animal (mouse), allow the disease to reproduce, reproduce death, culture their bacteria, and check to see if the identical microorganism is identified. This method is used to confirm the etiologic agent can cause infection and the potential outcome of that infection
Bacteria: Identification Microscopy: Using the time-tested technique of gram-staining, we can discern morphologies as well as susceptibilities. We are expected to know these groupings: (unless specified, these are aerobes) (+) = Purple, (-) = Red
- Cocci o (+): Staph. aureus, Staph. Epidermidis, Streptococci o (-): Gonococcus, Meningococcus
o (-): Bacteroides, Hemophilus, Fusobacterium, Acinetobacter, Pseudomonas, and the Enterobacteraciae grouping: E. coli, Enterobacter, Klebsiella
- Anaerobes: Bacteroides spp., Clostridium spp., Petostreptoccus - Once the microbe is identified, we use susceptibility tests to determine which method of control is most effective - The Next Steps: Growth on enrichment, selective, differential, or characteristic media. Specimen Biochemical
Test (rapid test methods). Immunological Techniques. Molecular (genotypic) Methods Virus: Discerning “The Flu” from “The Common Cold”
- Influenza [Viral Infection] o Timeline: Infected persons are contagious for up to 7
days, with a cough lasting potentially for weeks - Common Cold [Viral Infection]
o There are more than 200 different viruses known to cause the common cold, most frequent are Rhinoviruses, Coronaviruses, and Respiratory syncytial virus (RSV).
o Tx: None. ‘Tincture of time’ - Inappropriate Abx Tx: Both of these conditions are viral. Taking abx will only be
harmful. In fact, taking an abx can negatively impact the microbiome for between 1 month and 2 years before it can reconstitute. The microbiome is a part of our normal daily living
o **Leads to (1) Resistance and (2) Adverse Events Fungi: Fungal infections are quite rare, but are starting to become more common. In lecture, these slides were completely different. FYI, dermatophytosis is the most common fungal infection (toes)
- Yeasts (Candida spp.): Single-celled fungi. Found in moist environments, such as the GI tract and female genitals
- Molds (Aspergillus): Multicellular. Found in soil, food, and decomposing organic matter - Dimorphic fungi (Blastomyces, Histoplasma): Capable of growing as a yeast or mold
Parasite: Protozoan and Helminthic parasites are found worldwide, however more frequently occur among those living in rural, underdeveloped, or overcrowded places. WHO: ‘10% of the developing world is infected with intestinal worms’
- Parasitism: Ecological relationship between two different organisms, the parasite is physiologically or metabolically dependent upon the host ---- all major groups of animals have specific parasitic members
- Ascaris lumbricoides: Most common intestinal worm infection, ‘Giant Round Worm’. 1/6th of the world pop is infected by Ascaris. It is associated with poor hygiene, sanitation, and place where human feces is fertilizer. -.-
- Trichinosis: Caused by the parasitic roundworm (nematodes). Comes from eating raw or undercooked pork and wild-game. Contaminated meat often has the larvae Trichinella spiralis. This is not contagious, unless a human eats another human’s muscle (where the parasite persists)
Protozoans: Unicellular eukaryotic organisms responsible for diseases most often acquired when going camping - Diseases: Ameobiasis, Chagas’s disease, Malaria, African Sleeping sickness, Leishmaniosis, Toxoplasmosis
o Over the course of human existence, Malaria is projected to have infected 50 billion of 100 billion lives. - Ameobiasis (Amebic Dysentery): Caused by Entamoeba histolytica, this pathogenic amoeba is most often
encountered by travelers of tropics and subtropics with poor sanitization. (Flagyl is the mainstay tx) o Epidemiology: Prevalence 10-50%, it is the 2nd leading cause of mortality by parasitic disease in humans
- Giardia Enteritis (BeaverFever): Caused by the protozoal parasite Giardia intestinalis. Prions: “Infectious proteins”. These are not micro-organisms, just infectious particles often affecting the brain
- Mad Cow Disease: Bovine Spongiform Encephalitis. Causes neurons to rapidly degenerate. Food-Borne: It is estimated that, in the US alone, 76 million become sick from foodborne illnesses, hospitalizing 325k
- Ex: Salmonella, Campylobacter, E. coli, Listeria, Clostridium botulinum, Norovirus (1/29) Danziger Lecture: Introduction to Infectious Disease Epidemiology Recent Trends
- All diseases are on the rise again. It has been suggested that there is a cyclical phenomenon that epidemiology has yet to accurately discern. The major problem is that we do not know for sure
- Methicillin Resistant Staphylococcus aureus (MRSA): First described in the UK in 1961, MRSA has begun to dominate the total number of Staph-related infections due to its prolific drug-resistance
- Pertussis: On the rise, likely due to the new low-efficacy DTaP vaccine. Dramatic increase in cases 2012-2013
![Entamoeba histolytica / E. dispar - qu.edu.iqqu.edu.iq/vmjou/wp-content/uploads/2015/01/Vol.-111-8-14.pdf · [Entamoeba histolytica / E. dispar] ... Entamoeba histolytica trophozoite](https://static.documents.pub/doc/80x56/5aa7ee767f8b9ab8228ce260/entamoeba-histolytica-e-dispar-queduiqqueduiqvmjouwp-contentuploads201501vol-111-8-14pdfentamoeba.jpg)
![Entamoeba histolytica - Near East Universitydocs.neu.edu.tr/staff/serdar.susever/20entemoeba [Uyumluluk Modu]_119.pdfEntamoeba histolytica Entamoeba: cell biology, disease, and treatment](https://static.documents.pub/doc/80x56/5e2b9a0a3cd62723c411ced3/entamoeba-histolytica-near-east-uyumluluk-modu119pdf-entamoeba-histolytica.jpg)
