Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
331 Cards in this Set
- Front
- Back
|
List five 1st line agents used to treat Tuberculosis.
|
Isoniazid
Rifampin Pyrazinamide Ethambutol Streptomycin |
|
|
List nine 2nd line agents used to treat Tuberculosis.
|
Amikacin
Ciprofloxacin Levofloxacin Rifabutin Rifapentine Ethionamide Cycloserine Capreomycin Aminosalicylic acid |
|
|
What three agents are used primarily for Leprosy?
|
Rifampin
Clofazimine Dapsone |
|
|
Which anti-myobacterial drug inhibits mycolic acid synthesis? List first line and alternate.
|
Isoniazid
Alternate: Ethionamide |
|
|
Which anti-mycobacterial drug inhibits bacterial RNA polymerase? List first line and alternate.
|
Rifampin
Alternate: Rifabutin, Rifapentine |
|
|
Which anti-mycobacterial drug inhibits arabinoglycan synthesis?
|
Ethambutol
|
|
|
Which anti-mycobacterial drug probably acts by inhibiting fatty acid synthesis?
|
Pyrazinamide
|
|
|
Which anti-mycobacterial drug inhibits bacterial protein synthesis? List first line and alternate.
|
Streptomycin
Alternates: Capreomycin, Amikacin |
|
|
Which anti-mycobacterial drug inhibits bacterial folate synthesis? List first line and alternate.
|
Dapsone
Alternates: p-aminosalicylic acid |
|
|
What anti-mycobacterial drug inhibits bacterial DNA synthesis? List first line and alternate.
|
Clofazamine
Alternates: Ciprofloxacin, Levofloxacin |
|
|
What anti-mycobacterial drug is a cell wall synthesis inhibitor?
|
Cycloserine
|
|
|
What does the mnemonic RIPES stand for?
|
The order in which the first line antimycobacterial drugs are used
Rifampin-Isoniazid, plus Pyrazinamide, plus Ethambutol or Streptomycin |
|
|
Which of the 1st line RIPES is administered IV/IM? PO?
|
IV/IM - Streptomycin (in cases of meningitis, disseminated TB)
PO - Rifampin-Isoniazid, Pyrazinamide, Ethambutol |
|
|
Which are the two most active of the first line antimycobacterial drugs?
|
Rifampin and Isoniazid
|
|
|
What is the cure rate for susceptible TB drugs after a 9 month regimen of Rifampin-Isoniazid?
|
95-98%
|
|
|
Why would one add Pyrazinamide to a Rifampin-Isoniazid regimen?
|
Pyrazinamide is able to increase the overall efficacy and thus shorten the duration of the treatment as a whole. Pyrazinamide is typically administered for the first two months of the combination treatment.
|
|
|
In practice, how many drugs should be used to treat M. tuberculae infections?
|
Four - Rifampin, Isoniazid, Pyrazinamide, and Ethambutol OR Streptomycin
|
|
|
What is the approximate resistance to Isoniazid in the US?
|
~10%
|
|
|
What is the approximate resistance to Rifampin-Isoniazid in the US?
|
~3%
|
|
|
What bacteria is Rifampin effective against?
|
Gram + and Gram - cocci, some enteric bacteria, mycobacteria, chlamydia
|
|
|
If an organism develops resistance to Rifampin, what other two drugs will it have cross-resistance to?
|
Rifabutin
Rifapentine |
|
|
What mutation confers resistance to Rifampin?
|
Mutations in the rpoB gene - the Rifampin is no longer able to bind to the b-subunit of the bacterial DNA-dependent RNA polymerase and thus inhibit RNA synthesis.
|
|
|
Is Rifampin bactericidal or bacteriostatic to Mycobacteria?
|
Bactericidal
|
|
|
Under what circumstances do Rifampin, Streptomycin, and Ethambutol cross the BBB into the meninges?
|
When there is inflammation of the meninges
|
|
|
What are the toxicities of Rifampin?
|
Orange urine, sweat, tears, sometimes contacts
Rashes Thrombocytopenia Nephritis Hepatitis Cholestatic Jaundice Flu-like Symptoms |
|
|
How does Rifampin affect CYP 450?
|
Rifampin is a CYP 450 INDUCER, so it decreases plasma levels of the following drugs: anticoagulants, methadone, OCP, cyclosporine, PI, NNRTI, anticonvulsants
|
|
|
What structure does Isoniazid mimic? What are the consequences of this?
|
Isoniazid is very similar to Pyridoxine, but as a result it increases the rate of excretion of Pyridoxine and there is neuropathy and CNS toxicity (memory loss, psychosis, seizures)
|
|
|
How does Isoniazid affect Phenytoin?
|
It increases the plasma concentrations of Phenytoin, thus increasing its toxicity.
|
|
|
How common is peripheral neuropathy in patients taking Isoniazid?
|
10-20% (mostly at moderate-high doses)
|
|
|
What genetic condition(s) may affect metabolism of Isoniazid?
|
Slow vs Medium vs Fast Acetylators
Slow acetylators are more likely to suffer peripheral neuropathy. |
|
|
What are some adverse effects to Isoniazid?
|
Fever
Rashes DRUG INDUCED SYSTEMIC LUPUS ERYTHEMATOSIS Hepatitis (one of the more common ones) - S/S include anorexia, N/V, Jaundice, RUQ pain in about 1% of patients |
|
|
What is the primary clinical indication for Isoniazid?
|
Tuberculosis
|
|
|
What is the process by which Isoniazid inhibits tubercle bacilli, and exerts its bactericidal effect?
|
It inhibits mycolic acid synthesis, and mycolic acid is a key component of Mycobacteria cell walls. Isoniazid starts out as a prodrug which must be activated by KatG (mycobacterial catalase-peroxidase)
Mutations that overproduce inhA result in more NADH-dependent acyl carrier protein reductases. |
|
|
How do the activity requirements for Pyrazinamide effect inhibition of the tubercle bacilli and cause extra and intracellular effects?
|
The Pyrazinamide is most active at pH 5.5, lower than plasma but about the pH found inside lysosomes. The drug can then enter macrophages that contain otherwise inaccessible, difficult to destroy bacilli, become active via mycobacterial pyrazinaminase (encoded by pncA) conversion to Pyrazinoic Acid, and then it destroys the bacilli.
|
|
|
When would you decrease the dose of Pyrazinamide?
|
If a patient is on dialysis or has a decreased creatinine clearance.
|
|
|
What are the side effects related to Pyrazinamide?
|
Hepatotoxicity (1-5%), N/V, drug fever, hyperuricema (may cause an acute gout flare up)
|
|
|
What form is Ethambutol sold as?
|
A dihydrochloride salt
|
|
|
How does Ethambutol work, and how do Mycobacteria develop resistance?
|
Ethambutol inhibits mycobacterial arabinosyl transferases (encoded via embCAB) and thus arabinoglycan is inhibited, and the cell walls cannot be constructed.
Mutations that overexpress emb gene products or are within the embB structural gene result in resistance. |
|
|
What are the side effects for Ethambutol?
|
Retrobulbar Neuritis - loss of visual acuity, red-green colorblindness. Generally contraindicated in children because it may not be possible to do proper eye checks on them.
|
|
|
When would Streptomycin be used?
|
In the case that an anti-TB drug must be administered via injection, Streptomycin is a decent candidate.
The drug must be given IV/IM because it is a very severe infection, like TB meningitis and disseminated disease |
|
|
What are the side effects of Streptomycin?
|
Ototoxicity, Nephrotoxicity, vertigo, hearing loss, toxicity is dose related.
Increased risk in elderly, avoid using for more than 6 months. |
|
|
When would you adjust the dose of Streptomycin?
|
The dose should be decreased when there are renal problems
|
|
|
Can Streptomycin penetrate lysosomes or other cells to kill bacilli?
|
No, Streptomycin exerts its effects on extracellular bacilli most commonly.
|
|
|
How are URTI viruses transmitted?
|
Inhalation of respiratory droplets (sneezing, coughing)
Fomite - dried droplets - contaminate the hands, then transferred to mouth, eyes, nose. Lungs - infected from blood |
|
|
How does a virus cause sore throat?
|
Viral replication in the nasopharynx and activation of prostaglandins and the bradykinin system
|
|
|
How do viruses induce pruritis?
|
The body reacts by producing inflammatory cytokines - more common in influenza
|
|
|
How does a virus cause rhinorrhea?
|
With inflammation, capillary permeability increases, as do goblet cell secretion and plasma cell activity. Color change reflects recruitment of leukocytes.
|
|
|
How do viruses cause nasal congestion?
|
The body produces bradykinin in response to infection, resulting in vasodilation of vessels in the nasal epithelium.
|
|
|
How is sneezing caused?
|
Inflammation in the nose and nasopharynx act on the trigeminal nerve, relaying information to the brain's sneezing center
|
|
|
How are coughs caused?
|
Probably due to inflammation of the airways at the laryngeal level, and sensation of airway irritation, along with increased airway mucus production. Much more common in influenza than in the common cold.
|
|
|
Describe the Rhinovirus - family, capsule, genome?
|
Picornavirus family (mostly)
ssRNA genome Non-enveloped viruses |
|
|
When are Rhinovirus infections most common, and what percent of colds are they responsible for?
|
Responsible for 50-80% of all colds
Rhinovirus infections most common in spring and fall |
|
|
Are Rhinoviruses pH sensitive?
|
Yes, they are destroyed at pH 3
|
|
|
What area do Rhinoviruses target? How are they spread?
|
Rhinoviruses target the mucosa of the upper airways
Most likely transmitted by object-hand-face contact |
|
|
How does a Rhinovirus infection progress? Symptoms?
|
Symptoms develop 2-3 days after exposure
Symptoms include sneezing, rhinorrhea, mucosal inflammation and edema, headache, excessive mucus production, cough (30% of cases), sore throat Little or no fever May last 1-2 weeks |
|
|
What are Coronaviruses? Capsule, genome...
|
Enveloped
ssRNA genome |
|
|
What percent of common cold cases are caused by Coronaviruses?
|
15% of cases
Usually in winter, re-infection is common - symptoms indistinguishable from those of rhinoviruses |
|
|
What viruses in the Picornavirus family may cause the common cold?
|
Coxsackievirus
Parechovirus ssRNA genome, non-enveloped |
|
|
What are some sequelae of the common cold?
|
Otitis media
Conjunctivitis Laryngitis Bronchitis Asthma exacerbations Sinusitis Pneumonia Increased antibiotic resistance when children are treated with antibiotics for a viral URTI |
|
|
What are some preventive measures for the common cold?
|
HAND WASHING
Zinc salts Vitamin D |
|
|
What are some treatment measures for the common cold?
|
Treatment is for symptoms only - it doesn't help the body fight off, just makes the patient more comfortable
Chicken soup good; Vitamin C and Echinacea do NOT seem to do much Rhinorrhea - anticholinergics, 1st generation antihistamines Nasal congestion - intranasal and systemic decongestants Cough - nonspecific suppressants with codeine or dextromethorphan (1st gen antihistamines and NSAIDs may work better) Sneezing - antihistamines Sore throat, fever, myalgias, headache - mild analgesics, NSAIDs |
|
|
What are Orthomyxoviruses and influenza? Genome, capsule, etc.
|
Segmented ssRNA genome
Enveloped Divided into 3 groups - Group A, B, and C - groups defined by internal matrix proteins and ribonucleoproteins Subgroup serotypes determined by envelope proteins - neuraminidase, hemagglutinin Group A most significant - greater virulence, spread |
|
|
How does influenza progress?
|
Epidemics usually in winter
Incubation of 2-3 days, abrupt onset of fatigue, malaise, fever, headache, arthralgias, myalgias pharyngitis, dry cough, and some other S/S of URTI Acutely debilitating, self-limited - recover by day 7, fatigue and cough may last another 2-3 weeks |
|
|
How does hemagglutinin contribute to influenza virulence?
|
Important in viral attachment and fusion with cells
|
|
|
How does neuraminidase contribute to influenza virulence?
|
It cleaves sialic acid, thins mucus and aids in both viral binding and release and spread
|
|
|
What are H and N and how do they affect the influenza virus?
|
H = Hemagglutinin
N = Neuraminidase Both are proteins, virulence factors in the influenza virus envelope - different mutations and combinations of H and N result in different virulence and allow for regular epidemics. |
|
|
What is viral M2 protein?
|
A proton channel, required for viral uncoating and subsequent nuclear replication - found in influenza viruses
|
|
|
What are two mechanisms by which influenza A viruses mutate and cause new epidemics?
|
Antigenic Drift
Antigenic Shift |
|
|
What is antigenic drift?
|
Results from point mutations - resulting in altered structure of preexisting proteins in the virus.
|
|
|
What is antigenic shift?
|
Results from nucleic acid exchange between different viruses - only group A influenza undergoes antigenic shift.
When different viral strains exchange RNA segments, the virus is able to express a novel hemagglutinin and there is no cross-protective immunity. |
|
|
How does antigenic shift tend to happen? Give an example?
|
Animal viruses that never infect people inhabit an animal coinfected with a human virus, and the human virus acquires new proteins from the animal virus, becoming a novel virus to the human immune system.
|
|
|
How is influenza usually diagnosed?
|
Typically based upon clinical signs alone
|
|
|
What is the treatment for influenza?
|
Rest, fluids, antipyretics (acetaminophen in children)
|
|
|
How can influenza be prevented?
|
Killed tri- or tetravalent viral vaccines prevent the disease in the majority of people - must be updated yearly to reflect the new serotypes that are most abundant
Aerosol live trivalent attenuated virus vaccines appear to give better immunity to children |
|
|
What are two targets of anti-influenza medications?
|
Neuraminidase (NA)
M2 Protein - Ion Channel |
|
|
What are two M2 inhibitors?
|
Amantadine
Rimantadine |
|
|
What are two NA inhibitors?
|
Zanamivir
Oseltamivir |
|
|
To what do the viruses attach to induce endocytosis into a target cell?
|
Hemagglutinin glycoproteins attach to sialic acid on the target cell membrane
|
|
|
What do neuraminidases (aka sialidases) do?
|
They catalyze the hydrolysis of terminal sialic acid residues from the newly formed virions
|
|
|
Against what group of influenza are Amantadine and Rimantadine effective?
|
Influenza A (because M2 is different in Influenza B)
|
|
|
What is the effect of inhibiting M2 protein channels?
|
Prevents viral replication by blocking the M2 protein of the viral particle and inhibits uncoating of the viral RNA within infected host cells
|
|
|
How are M2 inhibitors used?
|
Chemoprophylaxis - against S/S of influenza A infection
Treatment of respiratory tract illness caused by influenza A virus strains - administered early in the course of illness. |
|
|
Describe the absorption, half life, excretion of Amantadine and Rimantadine.
|
Well absorbed PO
T1/2 = ~17h Primary excretion via kidneys - glumerular filtration and tubular secretion |
|
|
Recently, what is the resistance of the common influenza strains to Amantadine and Rimantadine?
|
100% of H3N2 was resistant
2009 pandemic flu samples have shown a lot of resistance |
|
|
What are some other uses for Amantadine and Rimantadine?
|
May be useful in reducing symptoms of Parkinson's disease - a dopaminergic effect
|
|
|
What are some adverse reactions to Amantadine and Rimantadine?
|
GI upset
CNS (dopaminergic effects) - anxiety, insomnia, difficulty concentrating Teratogenic potential (category C) Peripheral edema |
|
|
What are two Neuraminidase inhibitors?
|
Zanamivir
Oseltamivir |
|
|
Against what influenza virus groups are Neuramindase inhibitors effective?
|
Influenza A
Influenza B |
|
|
What are the uses for Neuraminidase inhibitors?
|
Influenza prophylaxis and treatment - take within 2 days of symptoms
|
|
|
How do Zanamivir and Oseltamivir work?
|
They inhibit neuraminidase (sialidase) and interfere with release of progeny influenza virus from infected new host cells - early administration is crucial)
|
|
|
How is Oseltamivir manufactured?
|
It is developed from shikimic acid - derived from Chinese star anis
|
|
|
How are Zanamivir and Oseltamivir administered? Any restrictions?
|
Zanamivir - must be inhaled - only in patients over 7 years old, avoid with asthma, COPD
Oseltamivir - well absorbed PO, only patients over a year old |
|
|
What are some side effects of Neuraminidase inhibitors?
|
Bronchospasm (Zanamivir)
GI symptoms (Oseltamivir) Psychological effects |
|
|
Name two anti-RSV drugs?
|
Palivizumab
Ribavirin |
|
|
What is RSV?
|
Respiratory Syncytial Virus, coated in sharp proteins - such as F-glycoprotein, G-glycoprotein
Common November to March |
|
|
What is targeted by Palivizumab?
|
F-Glycoproteins (fusion protein) on the surface of RSV
|
|
|
What is Palivizumab used for?
|
Prophylaxis for high risk infants for RSV
|
|
|
How does Ribavirin affect RSV?
|
It interferes with the synthesis of guanosine triphosphate and inhibits capping of viral mRNA, inhibits viral RNA polymerase.
|
|
|
How is Ribavirin absorbed? What affects absorption?
|
High availability PO, especially with high-fat meal
Decreased absorption with antacids |
|
|
When is Ribavirin used?
|
Support and treatment for children/infants with severe RSV bronchiolitis or pneumonia (aerosol)
Also for bronchopulmonary dysplasia (BPD) Standard treatment for HCV infection, in combination with peg IFN alpha-2a |
|
|
What are some adverse reactions of Ribavirin?
|
Hemolytic anemia
skin rash bronchospasm depression fatigue irritability nausea insomnia |
|
|
When is Ribavirin contraindicated?
|
Patients with uncorrected anemia
end-stage renal failure ischemic vascular disease pregnancy |
|
|
What is Palivizumab?
|
A humanized monoclonal antibody directed against an epitope in the A antigen site on the F fusion glycoprotein of RSV - blocks viral entry to hose cells.
|
|
|
What infants are considered high risk and subsequently treated with Palivizumab as RSV prophylaxis?
|
Prematurity
Chronic lung disease of prematurity Congenital heart disease Anything that affects the lung's ability to function properly |
|
|
What are some side effects of Palivizumab?
|
Anaphylaxis (hypersensitivity reaction)
Infections (URTI, otitis media) Skin reactions GI symptoms |
|
|
What are some major complications of influenza infections? What are causative organisms?
|
Secondary bacterial pneumonia - S. aureus, S. pneumoniae, and H. influenzae infections are most common.
S. aureus is most serious |
|
|
How does influenza facilitate bacterial infections?
|
The influenza virus destroys respiratory epithelial cells, making them vulnerable to bacterial colonization by S. pneumoniae, S. aureus, H. influenzae.
|
|
|
What is Reyes syndrome and how is it connected to influenza infections?
|
When kids get the flu, they tend to get a fever, and if aspirin is given to children there is a high risk of Reyes disease.
Reyes disease is an acute, often fatal non-inflammatory encephalopathy with fatty liver degeneration |
|
|
What is viral pneumonia?
|
May have high mortality rates in young adults and children, from pandemic viral pneumonia
|
|
|
What populations are at risk for complications of seasonal influenza?
|
Children < 1 year
Adults > 65 years Pregnant women People of any age with co-morbid illnesses - especially cardiopulmonary and neuromuscular disease Immunosuppressed/compromised patients |
|
|
What anti-influenza medications is H1N1 resistant to? susceptible to?
|
2009 H1N1 is resistant to Adamantine,
Susceptible to Oseltamivir and Zanamivir |
|
|
What are Parainfluenza viruses? What family, genome, capsule...
|
They are enveloped viruses
ssRNA genome Family Paramyxoviridae There are four known serotypes, most common are 1 and 3 They cause croup (acute laryngotracheobronchitis) |
|
|
How are Parainfluenza viruses spread?
|
Spread person to person via contact or exposure to respiratory droplets
|
|
|
Who are most often affected by Parainfluenza viruses?
|
Infants and young children, those <5 years old
|
|
|
What are the symptoms of croup, or Parainfluenza virus infections?
|
Symptoms similar to URTI which worsen with rapidly increasing hoarseness
Harsh barking cough Development of severe respiratory stridor Symptoms are worse at night |
|
|
What are some risks associated with croup?
|
Respiratory distress
Pneumonia Young age - more severe in children |
|
|
How are parainfluenza virus infections treated?
|
Dexamethasone (steroid) to reduce airway obstruction in moderate to severe cases
Cool moist air "mist therapy" in mild cases, plus analgesics Nebulized epinephrine, albuterol (for bronchodilation) |
|
|
What is Respiratory Syncytial Virus (RSV)? What family, capsule, genome?
|
Family Paramyxoviridae
Enveloped ssRNA genome |
|
|
What kind of illness do Respiratory Syncytial viruses cause?
|
Major cause of lower respiratory tract infections (LRTI) in young children - causes bronchiolitis, tracheobronchitis, pneumonia
|
|
|
What is the most common cause of hospitalization of young infants in the US?
|
Bronchiolitis (often caused by Paramyxoviridae viruses, like RSV)
|
|
|
How does an RSV infection progress?
|
Cold-like symptoms
Progresses to fever, cough, dyspnea, expiratory wheezing, rales, signs of respiratory distress (cyanosis) Also tachypnea, flaring of nostrils, intercostal chest wall retractions |
|
|
Describe RSV pneumonia
|
Similar to bronchiolitis, with interstitial mononuclear cell infiltrate, edema, possible necrosis and alveolar filling
|
|
|
What age group most often gets bronchiolitis? How common is it with RSV infections?
|
30-70% of RSV infections present with bronchiolitis
Bronchiolitis is most common in children < 6 months of age. |
|
|
How does RSV affect adults?
|
In typical adults, it is not too common and causes flu-like symptoms
Elderly and immunocompromised individuals are at higher risk |
|
|
Describe the pathogenesis of RSV.
|
RSV infects bronchiolar epithelium, leading to bronchiolar inflammation
Necrosis of bronchiolar epithelium Loss of cilia Peribronchiolar lymphocytic infiltration Edema and increased mucus production Occlusion of smaller bronchioles Envelope Glycoprotein G mediates viral attachment Envelope Glycoprotein F mediates penetration and syncytia formation |
|
|
What is Metapneumovirus? Family, capsule, genome?
|
Metapneumovirus is a member of Paramyxoviridae
Encapsulated ssRNA genome |
|
|
What does Metapneumovirus cause?
|
An important cause of mild-severe RTI in children - may account for 15% of acute bronchiolitis or LRTI - causes symptoms which are indistinguishable from RSV infection.
Most severe cases in first year of life - up to 90% of kids infected by age 5 |
|
|
What is Human Bocavirus?
|
HBoV - a member of the Parvoviridae family
Non-enveloped ssDNA virus |
|
|
What diseases are caused by Human Bocavirus infection?
|
Bronchiolitis
Bronchial pneumonia Associated with 5-19% of acute respiratory tract infections in children requiring hospitalization. |
|
|
What are the symptoms of Human Bocavirus infection?
|
Illness typified by fever, rhinorrhea, cough, and wheezing - most patients will have abnormalities seen on CXR - diagnosis via PCR. Symptomatic treatment only.
|
|
|
What is the second most common disease of childhood following URTI?
|
Acute Otitis Media
|
|
|
What is the most frequent reason for antibiotic therapy in the US?
|
Acute Otitis Media
|
|
|
What is the connection between AOM and URTIs?
|
AOM may closely follow URTI - viruses have been a factor in 17-50% of cases of AOM
|
|
|
What are the most common viral causes of AOM?
|
RSV
Parainfluenza virus Influenza virus Rhinovirus Other Picornaviruses Adenovirus |
|
|
What are some viral causes of laryngitis?
|
Adenoviruses
Influenza Parainfluenza Rhinoviruses RSV |
|
|
What is acute bronchitis?
|
Self-limited inflammation of the bronchi due to upper airway infection
|
|
|
What are the usual causes of acute bronchitis?
|
Influenza
Parainfluenza Coronavirus Rhinovirus RSV Human MPV |
|
|
What are some treatments for acute bronchitis?
|
Anti-tussives such as codeine and dextromethorphan are recommended for short-term relief, but not that effective
|
|
|
What percentage of cases of community-acquired pneumonia are from respiratory viruses?
|
20-25%
|
|
|
What respiratory viruses cause pneumonitis or viral pneumonia?
|
RSV
Metapneumovirus Influenza Adenovirus Human Bocavirus SARS Parainfluenza virus Varicella zoster Measles |
|
|
What kind of virus causes SARS?
|
Coronavirus
|
|
|
How did the H5N1 and Sin Nombre hantavirus cause disease?
|
Induction of pro-inflammatory cytokines - may lead to a cytokine storm causing alveolar compromise.
|
|
|
What really bad effect do the pandemic influenzas (H1N1 1918) cause in the lungs?
|
Alveolar and Bronchiolar Necrosis
|
|
|
What were the symptoms of SARS?
|
fever, chills, cough, and malaise. Approximately 70% of the patients subsequently suffered from shortness of breath and recurrent or persistent fever. Approximately 20-30% of these pts required intensive care treatment including mechanical ventilation.
|
|
|
What is Herpangina? What is the causative organism?
|
Also called mouth blisters, a painful mouth infection.
Caused most often by Coxsackievirus A (or Coxsackievirus B, echoviruses) |
|
|
How does Herpangina present and what is the most common patient demographic?
|
It may be asymptomatic, but also presents with fever, sore throat, mouth blisters in the back of the mouth - particularly soft pillars and tonsillar pillars. Ear pain, dysphagia. Lesions heal in 7-10 days.
Most often in children ages 3-10 |
|
|
What is Hand Foot and Mouth disease, and what is the causative organism?
|
A human syndrome caused by intestinal viruses of the Picornaviridae family - commonly Coxsackievirus A and Enterovirus 71.
|
|
|
How does Hand Foot and Mouth disease present?
|
Fever, often followed by sore throat. Loss of appetite, malaise, painful sores/lesions appear in the mouth and/or throat, rash may develop on the hands, feet, mouth, tongue, inside of cheeks. Diarrhea may lead to rash on the buttocks.
|
|
|
What is the most common patient demographic for Hand Foot and Mouth disease?
|
Children in kindergarten, nurseries tend to contract it. Very uncommon in adults.
|
|
|
What are some pathogens that cause Sinusitis and Otitis Media?
|
Streptococcus pneumoniae (20-35%)
Haemophilus influenzae (20-30%) Moraxella catarrhalis (20%) |
|
|
What are some pathogens that cause Pharyngitis?
|
Streptococcus pyogenes - strep throat
Corynebacterium diphtheriae - diphtheria |
|
|
What pathogen causes Epiglottitis?
|
Haemophilus influenzae
|
|
|
What pathogens are responsible for Pneumonia?
|
Streptococcus pneumoniae
Haemophilus influenzae Staphylococcus aureus Klebsiella pneumoniae Chlamydophila pneumoniae, psittaci Mycoplasma pneumoniae Legionella pneumophila Pseudomonas aeruginosa |
|
|
What pathogen causes Pertussis?
|
Bordetella pertussis
|
|
|
What pathogens cause Bronchitis?
|
Streptococcus pneumoniae
Haemophilus influenzae Mycoplasma pneumoniae |
|
|
What pathogen causes Tuberculosis?
|
Mycobacterium tuberculosis
|
|
|
What pathogen causes Anthrax?
|
Bacillus anthracis
|
|
|
List a few defense mechanisms of the respiratory tract.
|
Aerodynamic factors
The epiglottis and cough reflex Ciliated respiratory epithelium In the alveoli: macrophages, humoral factors (Ig, complement), neutrophils assist in clearing infection |
|
|
What are the characteristics of Moraxella catarrhalis?
|
Gram negative
Diplococci Aerobic Family: Neisseriaceae |
|
|
Where are Moraxella catarrhalis found, how are they transmitted, and what diseases may they cause?
|
Commensal of the URT
Transmission via respiratory droplets Causes 20% of Otitis Media and sinusitis in children May cause bronchitis or pneumonia in people with underlying chronic lung disease May cause bacteremia in immunocompromised patients |
|
|
How is Moraxella catarrhalis diagnosed? What laboratory tests?
|
Sinus or bronchial secretion, sputum sample
Gram stain - a large number of Gram negative diplococci Culture - fastidious growth on enriched media, eg. blood or chocolate agar Often confused with Neisseria sp. |
|
|
How is Moraxella catarrhalis treated?
|
Antibiotic of choice is Amoxicillin
Alternative - Amoxicillin-Clavulanic acid, 2nd or 3rd generation cephalosporins, or TMP-SMZ Most are resistant to beta-lactamase (penicillins) |
|
|
If patients discontinue their antibiotic regimen for Strep throat, for what disease are they at higher risk?
|
~3% develop rheumatic fever
|
|
|
What disease is caused by Streptococcus pyogenes, and where does the organism live?
|
It causes Strep throat in humans, and rheumatic fever
It's only reservoir is humans - in the nasopharynx and skin Reservoir: infected individuals, 20% of school-aged children are carriers Transmitted via respiratory droplets |
|
|
What are some characteristics of Streptococcus pyogenes?
|
Gram positive cocci in chains or pairs
Catalase NEGATIVE Non-motile, non-spore forming Beta-hemolysis on blood agar Group A antigen Bacitracin-sensitive |
|
|
What are some virulence factors that increase adherence and protection of Streptococcus pyogenes?
|
M-protein - binds to fibronectin that coats the cells of the oropharynx, also antiphagocytic - prevents opsonization via complement
F-protein - binds fibronectin that coats the cells of the oropharynx Hyaluronic acid capsule - non-immunogenic |
|
|
What are some virulence factors that increase spread and damage dealt by Streptococcus pyogenes?
|
Streptolysins - pore forming, initiate host cell lysis
Exo-enzymes - DNAse, hyaluronidase, hemolysins Teichoic acids - inflammatory response |
|
|
How do phage encoded superantigens complicate a Streptococcus pyogenes infection?
|
The superantigen is expressed by the host bacteria, resulting in massive release of cytokines
Scarlet fever (there is diffuse erythematous rash, scarlatiniform rash (sandpaper rash, strawberry tongue)) and Streptococcal Toxic Shock Syndrome may both result |
|
|
How is Streptococcus pyogenes infection diagnosed?
|
Throat swab is taken
Rapid strep test - enzyme immunoassay - very specific Culture - beta-hemolytic colonies on blood agar, Bacitracin sensitive Microscopy - Gram positive cocci, short chains in clinical specimens, long chains in media Catalase negative |
|
|
How is Streptococcus pyogenes treated?
|
Self-limiting disease, but has to be treated to prevent negative sequelae
Antibiotic of choice - Penicillin Alternates - Macrolide like Erythromycin, Clarithromycin |
|
|
What is Corynebacterium diphtheriae?
|
A bacteria found worldwide which causes Diphtheria in unvaccinated individuals, mostly children. May be fatal, only about 0-5 cases per year in the US.
Humans are the only known reservoir |
|
|
How is Diphtheria transmitted?
|
It is carried by asymptomatic individuals, or infected persons.
It is transmitted via respiratory droplets |
|
|
What are the characteristics of Corynebacterium diphtheriae?
|
Gram positive, club-shaped spores
Non spore-forming Aerobic Non-motile Corynebacterium sp. are part of normal human flora Diphtheria toxin (coded by a bacteriophage) causes Diphtheria |
|
|
How does the Diphtheria toxin cause disease?
|
It is a heat labile A-B exotoxin
A subunit: ADP ribosyl transferase - transfers ADP-ribose to EF-2 and inactivates it, stopping transfer of amino acids from tRNA to the polypeptide chain. Thus it blocks protein synthesis and causes death of the target cell. The B subunit embeds in the cell membrane, induces endocytosis, and the A subunit causes the negative effects. |
|
|
How does the disease Diphtheria progress?
|
Mucosa of oropharynx becomes infected
Multiplication of bacteria and production of toxin Exotoxin activity leads to death of surrounding cells, necrosis Inflammatory reaction produces gray exudate, evolves into a thick pseudomembrane: fibrin, dead granulocytes, necrotic epithelial cells, and bacteria The coating/membrane may lead to obstruction of the airway and suffocation |
|
|
How does Diphtheria present?
|
Sudden onset
Sore throat, pharyngitis Malaise Low grade fever Thick pseudomembrane in throat Regional lymph nodes highly swollen - bull neck Potential respiratory obstruction |
|
|
What are the problems with systemic intoxication by Diphtheria toxin?
|
Directly damages heart and nervous system
Myocarditis and cardiac dysfunction Laryngeal nerve palsy Lower limb polyneuritis Death from respiratory obstruction or cardiac failure |
|
|
What tests are used to diagnose Diphtheria?
|
Pharyngeal swab
Microscopy is non-specific Cultures are necessary - plate on a selective tellurite medium. K tellurite inhibits accompanying flora, and is reduced to tellurite, which produces black colonies with dark halos. |
|
|
How is Diphtheria toxin detected?
|
Ekel immunodiffusion test - tests toxin production, the toxin is produced and diffuses away from the strain, antitoxin diffuses away. They form a precipitation line.
May also be detected via PCR for the tox gene |
|
|
What is the treatment for Diphtheria?
|
Antitoxin serum therapy
Supplemented by administration of antibiotic - best is Penicillin. Alternative: Erythromycin |
|
|
How is Diphtheria prevented?
|
Active immunization - Toxoid vaccine - formaldehyde with modified toxin, reduced toxicity.
Combination vaccines are used - DTaP, Tdap, DT, and Td |
|
|
What are some characteristics of Haemophilus influenzae?
|
Gram negative
Pleomorphic rods Encapsulated - serovar b (Hib) - main pathogenic form Requires growth factors X (hemin) and V (NAD, NADP) |
|
|
What is the reservoir for Haemophilus influenzae and how is it transmitted?
|
Reservoir is human nasopharynx
Transmitted via respiratory droplets |
|
|
What is caused by Haemophilus influenzae infection?
|
URTI and LRTI in individuals with weakened immune systems and children under 5. Meningitis and sepsis in small children.
|
|
|
What are some type b Haemophilus influenzae infections in unvaccinated children?
|
Epiglottitis
Pneumonia Meningitis Septic arthritis Cellulitis |
|
|
What are some infections caused by non-encapsulated Haemophilus influenzae?
|
Local infections in children - Otitis Media, Sinusitis, Bronchitis
|
|
|
What are some virulence factors for Haemophilus influenzae and how do they effect increased virulence?
|
Pili - mediate colonization
Lipopolysaccharide - inflammation IgA-protease - mucosal colonization Polysaccharide capsule - anti-phagocytic, type b = poly-ribitol-phosphate, more invasive and pathogenic than other strains. |
|
|
How are Haemophilus influenzae infections diagnosed?
|
Collect samples of CSF, blood, pus, purulent sputum
Microscopy - Gram negative coccobacilli or rods Culture - chocolate agar, satellite phenomenon - there is no growth on blood agar, except as satellite colonies surrounding S. aureus (because S. aureus produces V factor) |
|
|
What antigen is detected to diagnose Haemophilus influenzae?
|
Poly-ribitol-phosphate - present in serum, CSF, urine of more than 95% of Haemophilus influenzae type b meningitis cases.
May be tested via antibody-coated latex particles + clinical specimen = agglutination |
|
|
How are Haemophilus influenzae infections treated?
|
Serious infections - use 3rd generation cephalosporins - like cefotaxime, ceftriaxone.
For sinusitis/otitis media - amoxicillin + clavulanic acid |
|
|
How are Haemophilus influenzae infections prevented?
|
Hib conjugate vaccine - polysaccharide casule poly-ribitol-phosphate PRP + protein carriers = T-cell dependent vaccine; no protection against non-encapsulated strains.
|
|
|
What is Bordetella pertussis?
|
Bordetella pertussis is the causative organism in Pertussis, or whooping cough. It is found worldwide, there are vaccinations, but about 400,000 people die worldwide anyway.
|
|
|
What are some characteristics of Bordetella pertussis? How is it transmitted?
|
Gram negative
Coccobacillus Nutritionally fastidious Infects tracheobronchal epithelium Humans - only reservoir, spread via infected persons and asymptomatic carriers in respiratory droplets - highly communicable. |
|
|
How does Bordetella pertussis effect disease?
|
It is a pathogen of the mucosal surface, and attaches to ciliated epithelial cells in bronchi and trachea. It proliferates on the surface and results in immobilization of the cilia, resulting in accumulation of mucus.
|
|
|
What are some virulence factors associated with Bordetella pertussis?
|
Pertussis toxin - Ptx - A subunit ADP-ribosylates G-protein and increases adenylate cyclase activity, resulting in impaired chemotaxis, phagocytosis, and bactericidal activity. Increased capillary permeability --> local edema.
Toxin destroys ciliated cells resulting in inflammation and necrosis Tracheal cytotoxin (murein) also kills ciliated epithelial cells. |
|
|
What are the three stages of Bordetella pertussis infection?
|
Catarrhal stage
Paroxysmal stage Convalescent stage |
|
|
List a few atypical mycobacteria - they cause lymphadenitis, skin disease, disseminated disease, and TB-like pulmonary diseases.
|
Mycobacterium avium complex (avium, intracellulare)
Others: M. abscessus, M. chelonae, M. fortuitum, M. kansasii, M. xenopi |
|
|
What antibiotics are MDR-TB (Multidrug resistant TB) resistant to?
|
Isoniazid, Rifampin
|
|
|
What antibiotics are XDR-TB (extensive drug resistant TB) resistant to?
|
Resistant to Isoniazid, Rifampin
Also resistant to the best second line medications: fluoroquinolones, and at least three injectable drugs (amikacin, kanamycin, capreomycin) |
|
|
Which anti-mycobacterial drugs are capable of acting extracellularly and intracellulary (ie they may enter macrophages)
|
Isoniazid, Pyrazinamide
|
|
|
What is INH?
|
Isonicotinyl hydrazine - aka Isoniazid
|
|
|
What is RIF?
|
Rifampin
|
|
|
Which anti-mycobacterial drug increases plasma concentration of other drugs by inhibiting p450? Which drug induces p450 and decreases plasma concentration of other drugs?
|
Rifampin - a p450 inducer - decreased plasma concentration
Isoniazid - a p450 inhibitor - increased plasma concentration |
|
|
Which anti-mycobacterial drug is bacteriostatic?
|
Ethambutol
|
|
|
What is PZA?
|
Pyrazinamide
|
|
|
What is Rifater?
|
A fixed combination of Isoniazid-Rifampin and Pyrazinamide
|
|
|
What is 4-FDC?
|
A fixed combination of Isoniazid-Rifampin, Pyrazinamide and Ethambutol
|
|
|
Which anti-mycobacterial drug is an irreversible inhibitor of 30S ribosome?
|
Streptomycin
|
|
|
What category of drug is Streptomycin?
|
Aminoglycoside
|
|
|
What two anti-mycobacterial 2nd line agents are fluoroquinolones?
|
Ciprofloxacin
Levofloxacin |
|
|
When is Amikacin used?
|
Treats streptomycin-resistant TB
|
|
|
Ciprofloxacin and Levofloxacin used for TB? What is their MOA?
|
They inhibit DNA gyrase
They are active against M. tuberculosis, and atypical mycobacteria |
|
|
When is Rifabutin used in place of Rifampin?
|
Rifabutin is a less potent inducer of p450 and is used in place of rifampin to treat TB in HIV-infected patients who are receiving concurrent antiretroviral therapy.
This way, the antiretroviral drugs are not excreted more rapidly |
|
|
Which bacterial RNA polymerase inhibitor is a strong inducer of p450 and is avoided in HIV patients due to high relapse rates with rifampin-resistant TB?
|
Rifapentine
|
|
|
How does Cycloserine work in treating TB, and what are some adverse reactions?
|
Inhibits cell wall synthesis
Adverse reactions - peripheral neuropathy, CNS dysfunction - take with pyroxidine like INH |
|
|
What is the recommended treatment for acute TB?
|
INH-RIF PZA and Ethambutol for 2 months, then continue INH and RIF for 4-7 months
|
|
|
What is the recommended treatment for latent TB?
|
A 9 month regiment of INH
Rifampin may be combined with INH |
|
|
What drugs are used to treat M. avium complex?
|
Clarithromycin or Azithromycin + Ethambutol with or without Rifabutin
|
|
|
What category of drug are Clarithromycin and Azithromycin, which are used for atypical TB? What about Erythromycin?
|
Macrolides
Erythromycin is in the same category, but Erythromycin is better in some cases because it does not inhibit p450 enzymes but it is not as acid stable. They bind to 50S ribosomes |
|
|
Describe Tuberculoid leprosy.
|
Also known as Paucibacillary leprosy or PB leprosy
A milder form, in which bacteria live in a few small symmetrical skin lesions |
|
|
Describe Lepromatous leprosy.
|
Also known as Multibacillary leprosy or MB leprosy
The severe form in which skin lesions are numerous in size and larger. |
|
|
What drugs are used to treat PB leprosy?
|
Rifampin
Dapsone |
|
|
What drugs are used to treat MB leprosy?
|
Rifampin
Dapsone Clofazimine |
|
|
How does Dapsone work? What are some adverse effects?
|
It inhibits folate synthesis by inhibiting dihydropteroate synthetase
Hemolysis (especially in patients with G6PDH deficiency) Erythema nodosum leprosum (ENL - can be suppressed by thalidomide or corticosteroids) |
|
|
What other drugs have a similar MOA to Dapsone?
|
Sulfamethoxazole (dihydropteroate synthetase inhibitor)
Trimethoprim (dihydrofolate reductase inhibitor) |
|
|
If Dapsone is ineffective or contraindicated, what drug may be used in its place and what are its side effects? Is there anything it specifically treats?
|
Clofazimine may be used - a phenazine dye
Lipophilic - accumulates in fatty and reticuloendothelial tissues Used for sulfone-resistant leprosy or when patients are intolerant to sulfones - useful in treating erythema nodosum leprosum Adverse reactions - GI intolerance, dry skin, discoloration |
|
|
Describe the Catarrhal stage of Pertussis.
|
Lasts 1-2 weeks, similar to the common cold
Highly communicable |
|
|
Describe the Paroxysmal stage of Pertussis.
|
Lasts 2-4 weeks
Paroxysmal cough separated by inspiratory whoop Mucus production, vomiting, convulsions, cyanosis Severe coughs can cause neurological damage and eye hemorrhages |
|
|
Describe the Convalescent stage of Pertussis.
|
Cough episodes slowly decrease, gradual recovery - weeks to months
|
|
|
What are some complications associated with Pertussis?
|
Secondary pneumonia - superinfection with Streptococcus pneumoniae
Seizures, Hypoxia, Encephalopathy, Malnutrition |
|
|
Can vaccinated patients still get Pertussis?
|
In afebrile, vaccinated adults, about 20% of coughs lasting more than 2 weeks are caused by Bordetella pertussis.
|
|
|
How do you diagnose Pertussis based on laboratory findings?
|
From a nasopharyngeal swab...
Culture on selective Charcoal-blood agar Direct fluorescence antibody test |
|
|
How is Pertussis treated?
|
Azithromycin or Clarithromycin
During the catarrhal or early paroxysmal stages - prevents further spread and may be used as chemoprophylaxis for household contacts |
|
|
Describe the Pertussis vaccine.
|
An acellular pertussis vaccine - new, purified, inactivated components (Fha&Ptx) of B. pertussis, part of DTaP (Diphtheria, Tetanus, Pertussis)
|
|
|
Describe Tuberculosis - how many people are infected, how many die per year, how many cases involve resistant strains?
|
2 million die per year
2 billion estimated to be infected 1/10 cases involve a resistant strain 1/100 involve MDR strains XDR-TB is MDR + resistance to fluoroquinolones and IV streptomycin alternates |
|
|
Describe Mycobacterium tuberculosis - staining, shape, etc.
|
Acid-fast bacteria
Rod-shaped Obligate aerobe Non-spore forming Non-motile Very slow growth Facultative intracellular pathogen - able to establish long life infection. |
|
|
What are atypical mycobacterium? Where do they come from?
|
They are usually acquired from the environment
They have a low level of pathogenicity |
|
|
Describe the effects of infection with M. avium-intracellulare and M. kansasii.
|
Cause pulmonary TB-like or GI diseases
Disseminated disease in AIDS patients Transmission via inhalation or ingestion Opportunistic infections in immunosuppressed patients |
|
|
Describe the pathogenicity of M. bovis.
|
Causes TB in cattle but can also infect humans
Transmission via infected milk or aerosol droplets |
|
|
Describe the pathogenicity of M. scrofulaceum.
|
Causes lymphadenitis
Transmitted via contaminated water |
|
|
Describe the pathogenicity of M. marinum.
|
Causes soft tissue infections - fish tank granulomas
Transmission through abrasion |
|
|
Describe the cell wall of Mycobacteria and how it makes it so difficult to kill.
|
Unique among prokaryotes - waxy, hydrophobic, high lipid content.
Major determinant of virulence Peptidoglycan + complex lipids Responsible for slow growth, resistance to drying and chemical disinfectants, common antibiotics, osmotic lysis via complement deposition, lethal oxidation (macrophages), traditional stains and dyes Sensitive to heat and UV light |
|
|
What are some virulence factors of Mycobacteria?
|
Sulfolipids - inhibit phagosome-lysosome fusion
Cord factor - trehalose mycolate - inhibits leukocyte migration, disrupts mitochondrial respiration, serpentine cord colonies Tuberculin and Mycolic acid - delayed hypersensitivity and CMI - granulomas and caseation mediated by CMI Lipoarabinomannan - analagous to LPS |
|
|
Do Mycobacteria produce any exotoxins or endotoxins?
|
No
|
|
|
How does Mycobacterium tuberculosis invade the body and establish a colony?
|
Inhalation of M. tuberculosis in aerosol dropets
Engulfed by alveolar macrophages where they survive and replicate Transport via macrophages to the lymph nodes Possible distribution to other tissues through blood and lymphatic system |
|
|
How does Mycobacterium tuberculosis effect disease?
|
The body develops a reactive inflammatory focus - strong cell-mediated immune response. T-cells, activated macrophages - kill infected macrophages
Antibody production is ineffective - bacteria cannot be killed by macrophages Tissue necrosis occurs due to the host immune response Granuloma formation occurs at primary infection site and affected lymph nodes (hilar lymph nodes of lungs) Tuberculin allergy develops in the host |
|
|
Of those with Primary TB, how many develop Latent TB? Progressive primary (active) TB?
|
90% develop latent TB (LTBI)
10% develop active TB when lesions break down and the infection spreads via lymph/blood |
|
|
How many people with LTBI will develop reactivation secondary TB?
|
About 10% - usually from impairment of the immune system.
|
|
|
Are skin tests, CXRs and sputum cultures positive or negative in Latent TB? Progressive TB? Secondary TB?
|
Latent TB - PPD+ CXR+/- Sputum-
Progressive Primary and Secondary TB - PPD+, CXR+, Sputum+ |
|
|
What lab tests confirm TB?
|
Ziehl-Neelsen stain - acid fast stain
Rapid presumptive test Culture - confirms diagnosis - grown on Lowenstein-Jensen medium (lipid-rich) for 3-6 weeks at 37 degrees C. Cultures can then confirm organism via PCR and be used to determine antibiotic susceptibility |
|
|
How do you differentiate M. tuberculosis cultures from other Mycobacterial cultures?
|
M. tuberculosis produces non-pigmented colonies, niacin, and heat-sensitive catalase.
|
|
|
Which adenoviruses most commonly infect the respiratory tract?
|
Human adenoviruses B and C
|
|
|
What is the morphology of adenoviruses?
|
Icosahedral (20 triangles 30 sides) , non-enveloped, dsDNA
|
|
|
What is Acute Respiratory Disease?
|
A sudden condition in which breathing is difficult and the oxygen levels in the blood abruptly drop lower than normal.
|
|
|
What is Pharyngoconjunctival fever?
|
An eye infection, a type of
follicular conjunctivitis seen along with respiratory symptoms in adenoviral infection - also associated with lymphadenopathy and fever. More often in individuals under age 18. |
|
|
What demographic is more likely to have adenoviral respiratory disease?
|
Young children
Military recruits? |
|
|
What diseases does Streptococcus pneumoniae cause?
|
It is the main cause of bacterial community-acquired pneumonia
Most common cause of otitis media and sinusitis in children and adult meningitis Bacteremia |
|
|
What is the reservoir for Streptococcus pneumoniae and how is it transmitted?
|
Human throat and nasopharynx
Transmitted via respiratory droplets from infected persons, asymptomatic carriers, or opportunistic infection |
|
|
What are some predisposing conditions for contracting Streptococcus pneumoniae?
|
Age - children and elderly - especially after a viral RTI
Chronic diseases - COPD, diabetes, renal problems, alcoholism Immunocompromised patients |
|
|
Describe Streptococcus pneumoniae - morphology, characteristics...
|
Lancet-shaped
Gram + Diplococcus Catalase NEGATIVE Non-motile, non-spore forming Fermentation metabolism Alpha-hemolytic on blood agar Optochin sensitive Bile soluble - lysed by bile salts Surface capsule Not typeable |
|
|
How may a Streptococcus pneumoniae infection progress once it establishes itself in the nasopharynx?
|
Infect the lung, cause pneumoniae, bacteremia or meningitis
Infects the eustachian tube, causes otitis media |
|
|
What are some virulence factors of Streptococcus pneumoniae?
|
Polysaccharide capsule - essential - antiphagocytic
IgA protease - for colonization Autolysin - peptidoglycan hydrolase - release of intracellular virulence factors and cell wall fragments Pneumolysin - transmembrane pore-forming toxin - released and autolyzed, damages respiratory epithelium Peptidoglycan/teichoic acids - inflammation |
|
|
What is the typical onset and clinical presentation of lobar pneumonia?
|
Rapid onset
Chills and fever Productive cough and blood in the sputum (rusty sputum) Chest pain |
|
|
Describe "splinting" and in what disease is it most commonly found?
|
Because one lung is usually affected in lobar pneumonia, the pattern of breathing will have a patient reluctant to move one side of the chest due to pain.
It is termed "splinting" |
|
|
What laboratory tests are run to diagnose Streptococcus pneumoniae?
|
From a nasopharyngeal swab, sputum, blood or CSF...
Microscopy - Gram stain - positive diplococci, lancet-shaped Culture - Blood agar grows large mucoid colonies, alpha hemolytic, optochin sensitivity, bacitracin resistant Bile soluble Catalase negative |
|
|
Describe the Quellung reaction.
|
A quick test to identify S. pnuemoniae - capsular swelling occurs upon binding of homologous antibody
|
|
|
How are Pneumococcal (S. pnuemoniae) infections treated?
|
Penicillin resistance is common
3rd generation cephalosporins are used - cefotaxime, ceftriaxone For S. pneumoniae in otitis media, use amoxicillin + clavulanic acid |
|
|
How can Pneumococcal (S. pneumoniae) infections be prevented?
|
PPSV - pneumococcal polysaccharide vaccine - 23-valent polysaccharide vaccine
PCV - pneumococcal conjugate vaccine - 7-valent conjugated vaccine for children < 2 years old |
|
|
Describe Atypical/Walking Pneumonia.
|
Caused by Mycoplasma pneumoniae
Community acquired Found worldwide Primary atypical pneumonia Leading cause of pneumonia in school-age children and young adults |
|
|
What are some characteristics of Mycoplasma pneumoniae?
|
The smallest, free-living bacteria and smallest genome
No cell wall - pleomorphic, resistant to cell wall synthesis inhibitors, not seen on Gram stain Sterols in membrane - but cannot synthesize them, require sterol for in vitro culture Extracellular pathogen - reservoir is human respiratory tract. |
|
|
What diseases are caused by Mycoplasma pneumoniae and how is it spread?
|
Tracheobronchitis
Primary atypical pneumonia "walking pneumonia" Spread via respiratory droplets |
|
|
How does Mycoplasma pneumoniae establish itself in a human host?
|
It is a surface parasite, not invasive, so...
It adheres via P1 Adhesin to respiratory epithelial cells Inhibits ciliary action and protection |
|
|
How does Mycoplasma pneumoniae avoid host defenses?
|
Bacteria lodges between microvilli and cilia - prevents phagocytosis
|
|
|
How does Mycoplasma pneumoniae effect disease?
|
It damages the respiratory epithelia
Toxic metabolic products - hydrogen peroxide, superoxide radicals, cytolytic enzymes Ciliastasis and respiratory epithelial desquamation Prominently lymphocytic inflammatory response Disease rarely fatal - slow. |
|
|
Describe the progression of pneumonia caused by Mycoplasma pnuemoniae.
|
Incubates for 2-3 weeks following infection
Fever, headache, malaise Persistent hacking cough - dry or little sputum Cracking sound in the lungs CXR reveals patchy infiltrate suggestive of bronchopneumonia |
|
|
How are Mycoplasma pneumoniae infections diagnosed?
|
Gram stain - ineffective!
Culture from throat washings or sputum on Eaton's media because they require sterols - slow growth - generation time is 6 hours Serological tests (most common) - complement fixation test for antibodies to M. pneumoniae, ELISA or immunofluorescence. Cold agglutinins - agglutinate at 4 degrees C but not 37 degrees. PCR may also be used |
|
|
How are Mycoplasma pneumoniae infections treated?
|
Azithromycin or Clarithromycin
|
|
|
Describe Atypical Pneumoniae caused by Chlamydophila pneumoniae.
|
Found worldwide
All ages at risk, but most common in school-age children Common but usually not severe |
|
|
Describe Chlamydophila pneumoniae - morphology, stages, etc.
|
Small obligate intracellular pathogen
Found in two stages: Elementary body - EB - infectious, survives outside the host, nonreproductive particles. 0.3 micrometers Reticulate body - RB - noninfectious, intracytoplasmic, reproductive form. 1.0 micrometers. Gram negative - not visible on Gram stain Cell wall lacks peptidoglycan Unable to make their own ATP - energy parasites |
|
|
How does Chlamydophila develop (six steps)?
|
1. Host cell ingests an elementary body by endocytosis
2. No phagosome-lysosome fusion - EB differentiates to form a reticulate body 3. RB replicates by binary fission to form a mature inclusion 4. RB cells may adopt a non-replicating noninfectious persistent form 5. RB cells may alternatively redifferentiate into EBs (infectious) 6. EBs released by lysis of host cell, allowing other cells to be infected |
|
|
Describe the Elementary Body stage of Chlamydophila.
|
Infectious form
0.3-0.4 micrometers across Rigid outer membrane, extensive cross-linking by disulfide bonds Resistant to harsh environmental conditions when outside eukaryotic host cells |
|
|
Describe the Reticulate Body stage of Chlamydophila.
|
Non-infectious
Intracellular Metabolically active Replicating form of Chlamydophila Fragile membrane compared to EB |
|
|
What is the reservoir for Chlamydophila pneumoniae and how is it transmitted?
What infectious does it cause? |
Reservoir - infected humans
Transmission via respiratory droplets Common infections of URT and atypical pneumonia - but clinically silent infections are common |
|
|
How does Chlamydophila pneumoniae progress from a silent to a symptomatic disease? What are some sequelae of infection?
|
Patient may develop pneumonia or bronchitis, with gradual onset of cough, malaise, and little or no fever
It may be associated with atherosclerotic vascular diseases |
|
|
How is Chalmydophila pneumoniae diagnosed?
|
Serological tests - complement fixation or immunofluorescence
Isolation is difficult (since it's embedded in the epithelia) |
|
|
How is Chalmydophila pneumoniae treated?
|
Macrolides - Erythromycin, Clarithromycin
Tetraclycines - Doxycycline |
|
|
What pathogen causes Psittacosis and what is the reservoir?
|
Chamydophila psittaci
About 50 cases/year in the US, natural reservoir is mainly birds - considered a Zoonotic pathogen |
|
|
Describe the pathogenesis of Psittacosis.
|
Inhaling dried secretions from infected birds allows organism into airway
Incubation period of 1-3 weeks Organisms multiply and there is focal necrosis The infection spreads from the lungs --> blood stream --> liver and spleen --> replication and necrosis continues This pneumonia is often associated with hepatitis |
|
|
What are some clinical features of Psittacosis?
|
Asymptomatic infections are common
Flulike symptoms, dry cough Uncomplicated cases - subsides 5-6 weeks after infection Complicated cases - convulsions, coma, death (5%) |
|
|
How is Chlamydophila psittaci diagnosed?
|
Isolation from sputum in tissue culture (rarely done)
Serodiagnosis by complement fixation test Cytoplasmic inclusions seen on Giemsa or fluorescent-antibody-stained sputum or biopsy |
|
|
How is Chlamyodophila psittaci treated?
|
Doxycycline or Tetracycline
|
|
|
How are Chlamydophila psittaci infections prevented?
|
Birds are fed antibiotic supplemented food
No vaccine is available |
|
|
What is the organism behind Legionnaire's Disease? Prevalence?
|
Legionella pneumophila
Discovered in 1976 Severe form of legionellosis = atypical pneumonia About 25,000 cases/year in the US Death in 10-15% of cases |
|
|
Describe Legionella pneumophila - morphology, characteristics...
|
Water organisms - survive at 45 degrees C
Weakly Gram - rods Complex nutritional requirements Aerobic, motile 12 serogroups but serogroup 1 is most common Facultative intracellular pathogen - multiplies in macrophages |
|
|
What diseases are caused by Legionella pneumophila?
|
Legionnaire's disease
Pontiac fever Atypical pneumonia |
|
|
What groups are at risk of infection by Legionella pneumophila?
|
Elderly
Smokers with high alcohol intake Immunocompromised patients |
|
|
Where is Legionella pneumophila found? How is it spread?
|
It is a free living organism, a parasite of protozoa
Reservoir: biofilms in water sources Transmitted via inhalation of contaminated aerosols (air conditioning) - faucets, fountains, showers... NOT transmitted person to person! |
|
|
How does Legionella pneumophila establish itself and cause infection?
|
It attaches to alveolar macrophages - coiling phagocytosis
Prevents phagosome-lysosome fusion Replication occurs inside the phagosome Lysis of phagocytes - hydrolytic enzymes (phospholipases, proteases, phosphatases) Results in lung damage and inflammatory response |
|
|
How does Legionnaire's disease present clinically?
|
Incubation of 2-10 days
Fever and Chills Non-productive cough Chest pain Headache Mental confusion Diarrhea X-rays reveal patches of fluid accumulation (unilateral or bilateral) After 3-6 days, shock, respiratory failure |
|
|
How is Legionnaire's disease diagnosed?
|
Sputum, broncho-alveolar lavage, urine
Microscopy - Gram - but stains poorly Culture - Buffered Charcoal Yeast Extract (BCYE) - no growth on blood agar Requires L-cysteine, iron, pH 6.9 - slow growth, 2-5 days Urinary antigen test - for serogroup 1 only PCR detects RNA genes Direct Fluorescent Antibody test (DFA) |
|
|
How is Legionnaire's disease treated?
|
Macrolides (Azithromycin)
Fluoroquinolones (Ciprofloxacin, Levofloxacin) |
|
|
How is Legionnaire's disease prevented?
|
Disinfection of water systems (hyperchlorination, superheating)
|
|
|
Describe the symptoms of Pontiac fever.
|
Flu-like illness
Occurs in healthy persons Acute onset Symptoms - muscle aches and fever Self-limiting No treatment required Little or no tissue damage Recovery in 2-5 days |
|
|
What diseases are caused by Klebsiella pneumoniae?
|
Pneumonia (typical) in patients with alcoholism, COPD, diabetes
UTI - catheter-related, fecal contamination Septicemia - immunocompromised patients |
|
|
Describe Klebsiella pneumoniae - culture, staining, etc.
|
Enterobacteriaceae family
Gram - rod Lactose + Non motile Oxidase negative Large polysaccharide capsule - mucoid colonies |
|
|
What is the reservoir for Klebsiella pneumoniae and how is it transmitted?
|
A common commensal in the human colon and URT - often an opportunistic pathogen
|
|
|
What are some virulence factors of Klebsiella pneumoniae?
|
Capsule - cannot be phagocytosed
Endotoxin - fever, inflammation, shock |
|
|
How does Klebsiella pneumoniae damage the body?
|
Necrotic destruction of alveolar space leads to abscesses
Endotoxins causing fever, inflammation, shock |
|
|
How does infection with Klebsiella pneumoniae progress clinically?
|
Sudden onset
High fever Thick bloody sputum (currant jelly) |
|
|
How is Klebsiella pneumoniae infection treated?
|
3rd generation Cephalosporin - Ceftazidime
|
|
|
What is Pseudomonas aeruginosa and what diseases does it cause in what at-risk populations?
|
An opportunistic pathogen found worldwide
Immunocompetent individuals - eye infections associated with contact lenses, wound infections, swimmer's ear, hot tub folliculitis Burn patients - burn and lung infections Cystic Fibrosis patients - lung infections Leukemic/transplant/neutropenic patients - pneumonia, septicemia Nosocomial infections - lungs, urinary tract and wounds Intravenous drug abusers - endocarditis, osteomyelitis, arthritis |
|
|
Describe the characteristics of Pseudomonas aeruginosa.
|
Gram - rod
Aerobic Motile Able to adapt to minimal nutritional requirements Reservoir - ubiquitous in the environment, transient colonization of the human body Transmitted via respiratory secretions, direct contact, fomites |
|
|
What are some virulence and pathogenic factors of Pseudomonas aeruginosa?
|
Invasive and toxogenic
Attachment via pili and nonpilus adhesins Avoids host defenses with polysaccharide capsule - protection from phagocytosis. Biofilm layer. Endotoxin and inflammation with LPS Exotoxin A - an A-B toxin like that of Diphtheria, inhibits protein production and causes cell death Exoenzyme S - ADP ribosylation of other proteins Elastase - cleaves elastin, collagen, Ig, complement Alkaline protease - proteolysis Cytotoxin - pore-forming protein Hemolysins - destroys erythrocytes |
|
|
How does Pseudomonas aeruginosa infection progress in pneumonia? in LRTI in CF patients?
|
Pneumonia - rapid, destructive. Alveolar necrosis, vascular invasion, and bacteremia
LRTIs in CF - chronic infection, mucoid strains of P. aeruginosa, alternates between colonization of bronchi and bronchitis/pneumonia. Symptoms include fever, productive cough, weight loss, dyspnea, cyanosis |
|
|
How is Pseudomonas aeruginosa infection diagnosed?
|
Gram stain - negative
Grows well on most media Blue-green colonies - procyanin, pyroverdin or fluorescein Grow at 42 degrees C Fruity aroma (grape like) Mucoid - production of alginate slime Fluorescence under UV light |
|
|
How are Pseudomonas aeruginosa infections treated?
|
Resistant to many ABx - restricted permeability, mutation and plasmid mediated resistance
Antipseudomonal penicillin + aminoglycoside (gentamicin) |
|
|
How are Pseudomonas aeruginosa infections prevented?
|
Nosocomial infections prevented by proper aseptic techniques, careful cleaning etc.
Waterborne outbreaks prevented with adequate chlorination of pools and hot tubs |
|
|
In what individuals does Acinetobacter spp. cause what disease?
|
Immunocompromised patients get nosocomial infections from Acinetobacter - pneumonia, wound infections, UTIs, sepsis
|
|
|
How are Acinetobacter infections treated?
|
Usually in very ill patients, so consider case by case basis
May be highly resistant to penicillin and chloramphenicol |
|
|
Where is Acinetobacter found and describe it's morphology.
|
A Gram negative coccobacillus
Found in soil, water, sewage, animals, and normal skin and GI tract of patients and health care workers |
|
|
Describe Anthrax - where is it found, what causes it, significance?
|
Found worldwide
Classic zoonosis Occurs primarily in animals, herbivores Recognized as an occupational disease - rare in the US except when weaponized. Bacillus anthracis |
|
|
Describe Bacillus anthracis - morphology, characteristics...
|
Aerobic Gram + Rod
Spore-forming Non motile Polypeptide capsule Ubiquitous/zoonotic |
|
|
Describe the different kinds of Bacillus anthracis infections.
|
Contamination with spores
Dermal anthrax - 90-95% of cases Respiratory anthrax - "wool sorter's disease" - inhalation of spores, animal hair, wool, or weaponized GI anthrax - rare in humans, common in herbivores Sepsis - possible from primary infection focus |
|
|
Describe the pathogenesis of pulmonary anthrax.
|
Inhalation of anthrax spores - end up in pulmonary alveoli
Spores phagocytosed by alveolar macrophages, germinate and replicate Transport through pulmonary lymphatics to mediastinal lymph nodes Exotoxins - cause hemorrhage and edema in lymph nodes and mediastinum - causing mediastinal hemorrhagic lymphadenitis Pleural effusions, thickening of the bronchovascular bundles Bacteria in blood stream, septicemia, meningitis, death |
|
|
For what pathogen is mediastinal hemorrhagic lymphadenitis a consequence of infection?
|
Bacillus anthracis
|
|
|
What are the virulence factors of Bacillus anthracis?
|
Spore - infectious particle
Capsule - poly-D-glutamic acid, antiphagocytic Exotoxins - edema factor (EF) - adenylate cyclase; lethal factor (LF) - kills cells; protective antigen (PA) - mediates entry of EF or LF into eukaryotic cells; PA + EF = edema PA + LF = tissue necrosis |
|
|
On what plasmid are the virulence factors associated with Bacillus anthracis?
|
pX01 plasmid
|
|
|
What are the two stages of respiratory anthrax?
|
Stage 1 - asymptomatic for a while, 2 months or more. Nonspecific initial symptoms - fever, chills, cough, malaise, headache, vomiting, chest pain
Stage 2 - rapidly worsening fever, edema, enlargement of mediastinal lymph nodes (CXR), respiratory distress, cyanosis, shock If not treated, death within 3 days of initial stage 2 symptoms |
|
|
How is Bacillus anthracis identified?
|
Gram stain - positive, long rods, single paired or serpentine chains
Capsule - only in clinical specimens with DFA or methylene blue Spores - 3 day old culture, not in clinical specimens Culture - large nonhemolytic adherent colonies on blood agar DFA test for specific Bacillus anthracis cell wall polysaccharide PCR |
|
|
How is Bacillus anthracis killed?
|
Fluoroquinolones - ciprofloxacin
|
|
|
How is Anthrax prevented?
|
Cell-free vaccine - from culture filtrate - used in high-risk persons
Control of animal disease - vaccine in endemic regions Complete eradication unlikely because of spores |
