Week 5 Microbiology Summary PDF

IIIR Unit- EPOM – B Course Microbiology Week 2 summary Ali Sultan EPOM B Week 5 (IIIR week 2 summary) For the microbiology lectures: Respiratory Ba...

IIIR Unit- EPOM – B Course Microbiology Week 2 summary Ali Sultan EPOM B Week 5 (IIIR week 2 summary) For the microbiology lectures: Respiratory Bacterial Pathogens (1) 1) Streptococcus pyogenes: a. Microbiological features, b. virulence factors: - Hyaluronidase, collagenase, and streptokinase: the mucosal membranes of the pharynx are damaged by the release of a variety of exoenzymes and exotoxins. - Many strains of S. pyogenes can degrade connective tissues by using Streptokinase, which degrades fibrin, dissolving blood clots, leading to the spread of the pathogen. - Streptolysins that can destroy red and white blood cells. - M-protein in pathogenesis of rheumatic heart disease c. Diseases caused by the organism especially pharyngitis, scarlet fever, and skin infections. d. Sequelae (complications) that follow the infection by this organism specifically; Acute Rheumatic Fever and Post-Streptococcal Glomerulonephritis (PSGN) with special emphasis of the time on onset (1-3 weeks after acute infections), mechanism of diseases and features. e. Treatment: Antibiotic resistance is limited for this bacterium, so most β-lactams remain effective; oral amoxicillin and intramuscular penicillin G are those most commonly prescribed. f. Prophylaxis to prevent acute rheumatic fever: penicillin. 2) H. influenzae: a. Microbiological Features: Gram-negative, coccobacillary, facultatively anaerobic bacterium. b. Virulence factors especially the polysacchride capsule, allows the bacteria to resist phagocytosis and complement-mediated lysis in the nonimmune host. c. Encapsulated strains were classified based on their distinct capsular antigens. The six generally recognized types of encapsulated H. influenzae are: a, b, c, d, e, and f. d. The unencapsulated strains are almost always less invasive; they can, however, produce an inflammatory response in humans e. Serotype B involved in meningitis, epiglottitis. The polysaccharide vaccine against this seroptype (Hib vaccine) has reduce the incidence of meningitis in children since its introduction. f. Diagnosis: requires culturing on chocolate blood agar. Requires factor X (hemin) and V (NAD+). g. Drug resistance (remember the role of Beta lactamase produced by the organism in conferring resistance to beta-lactam antibiotics). Third generation cephalosporin 1 IIIR Unit- EPOM – B Course Microbiology Week 2 summary Ali Sultan such as ceftriaxone is a good drug to use for treatment of H. influenzae infection, especially meningitis because in patients with meningitis, the penetration rate through the inflamed blood brain barrier (BBB) is very high. 3) Bordetella Pertussis: Gram-negative, aerobic, pathogenic, encapsulated coccobacillus. Virulence factors: The following several factors play a role in the pathogenesis: a. Attachment of the organism to the cilia of the epithelial cells is mediated by a protein on the pili called filamentous hemagglutinin (FHA). b. Pertussis toxin stimulates adenylate cyclase by catalyzing the addition of adenosine diphosphate ribose—a process called ADP-ribosylation—to the inhibitory subunit of the G protein complex (Gi protein). This results in prolonged stimulation of adenylate cyclase and a consequent rise in cyclic adenosine monophosphate (AMP) and in cyclic AMP-dependent protein kinase activity. This results in edema of the respiratory mucosa that contributes to the severe cough of pertussis. The toxin also has a domain that mediates its binding to receptors on the surface of respiratory tract epithelial cells. It is an A-B subunit toxin. Pertussis toxin also causes a striking lymphocytosis in the blood of patients with pertussis. The toxin inhibits signal transduction by chemokine receptors, resulting in a failure of lymphocytes to enter lymphoid tissue such as the spleen and lymph nodes. Because the lymphocytes do not enter lymphoid tissue, there is an increase in their number in the blood The inhibition of signal transduction by chemokine receptors is also caused by ADP- ribosylation of the Gi protein. c. The organisms also synthesize and export adenylate cyclase (CyaA). This enzyme, when taken up by phagocytic cells (e.g., neutrophils), can inhibit their bactericidal activity. Bacterial mutants that lack cyclase activity are avirulent. d. Tracheal cytotoxin is a fragment of the bacterial peptidoglycan that damages ciliated cells of the respiratory tract. Tracheal cytotoxin appears to act in concert with endotoxin to induce nitric oxide, which kills the ciliated epithelial cells. e. Causes respiratory illness known as whooping cough, which is very contagious disease. f. Classical pertussis disease is divided into three stages: the catarrhal, paroxysmal, and convalescence stages. g. The paroxysmal phase, with the classical whooping cough, is the hallmark of the disease. Paroxysms may be followed by vomiting. Diagnosis: culture is considered the gold standard because it is the only 100% specific method for identification. Other tests that can be performed include polymerase chain reaction (PCR), direct fluorescent-antibody assay (DFA) of nasopharyngeal samples and serology. h. Treatment: - Supportive therapy is the mainstay of treatment in patients with active pertussis infection. - Oxygenation, breathing treatments, and mechanical ventilation should be provided as necessary. Infants should be carefully observed for apnea, cyanosis, or hypoxia. 2 IIIR Unit- EPOM – B Course Microbiology Week 2 summary Ali Sultan - Drugs: macrolide antibiotics (e.g., erythromycin, clarithromycin, or azithromycin) have been effective and constitute the mainstay of treatment for patients with pertussis as well as for postexposure prophylaxis (PEP). i. Vaccine: DTaP immunization of infants and children. 4) Corynebacterium diphtheriae: a. Is a club-shaped, gram-positive rod. b. Can be microbiota of the nasopharynx in some people. c. Transmission: Diphtheria is commonly transmitted in the droplets and aerosols produced by coughing. d. Pathogenesis: after colonizing the throat, the bacterium remains in the oral cavity and begins producing the diphtheria toxin that blocks protein synthesis of respiratory epithelial cells leading to cell death. Dead host cells, pus, red blood cells, fibrin, and infectious bacteria results accumulate as a of grayish exudate known as a pseudomembrane. The pseudomembrane can cover mucous membranes of the nasal cavity, tonsils, pharynx, and larynx. e. Diseases: two types of clinical infection: nasopharyngeal and cutaneous. f. Main manifestation is an upper respiratory tract infection, characterized by pharyngitis, fever, malaise, swelling of the neck and headache. Hypoxia may develop due to airway obstruction by the pseudomembrane; characteristic lesion marked by patch of greyish membrane with surrounding inflammation. g. Complications; Carditis, neurologic complications. h. How to diagnose: the presumptive diagnosis of diphtheria is primarily based on the presence of the pseudo-membrane and isolating the causative agent by culturing throat swabs. The diphtheria toxin itself can be directly detected in vitro using polymerase chain reaction (PCR)-based. i. How to treat: Penicillin and erythromycin tend to effectively control C. diphtheriae infections. However, these antibiotics have no effect against preformed diphtheria toxin. Antitoxin (preformed antibodies against the toxin) is administered. j. Vaccination: widespread vaccination efforts have reduced the occurrence of diphtheria worldwide. There are several combination toxoid vaccines available that provide protection against diphtheria and other diseases; DTaP consisting of diphtheria, tetanus, and pertussis toxoids is commonly used to immunize children. Respiratory Bacterial Pathogens (2) For the second lecture (pneumonia) please focus on the following issues: 1) Definition of types of pneumonia (CAP vs HAP, VAP) 2) Typical vs atypical organisms involved. 3) Aspiration pneumonia: definitions and types 4) Pneumonia: Modes of infections 5) Pneumonia: High Risk groups 3 IIIR Unit- EPOM – B Course Microbiology Week 2 summary Ali Sultan 6) Clinical manifestations of pneumonia in neonate, adults, and elderly, 7) Diagnostic methods. 8) Organisms: focus on studying the following organisms and the features of pneumonia that caused by these organisms. In addition, the diagnostics features and how to treat and prevent infections caused by the following organisms: a. Streptococcus pneumoniae b. Klebsiella pneumoniae c. Staph aureus (pay special attention to pneumonia) d. Mycoplasma pneumoniae e. Legionella pneumophila f. Pneumocystis jirovecii Bacterial Genetics lectures: In regard to the bacterial genetics lecture given by Dr. Barany please focus on the following issues: 1- Regulation of expression by negative control (repression of the lac Opern). 2- Regulation of expression by positive control (CAP and CAMP) 3- Regulation by attenuation (Trp and mRNA hairpins). 4- Regulation by translation control. (in addition to the notes from Dr. Barany’s lecture, please see notes on bacterial gene regulations+MCQs posted in the microbiology supplemental section in Elentra) PBL drugs summary: Phenobarbital, a member of the class of barbiturates. Pharmacologic effect: CNS depressant. Pharmacokinetics: well-absorbed orally, mostly metabolized by cytochrome P450 (CYP) enzymes with a long half-life (about 4-5 days); some excreted unchanged. The fraction excreted unchanged depends on urine pH. The more alkaline the urine the more unchanged phenobarbital is excreted. Phenobarbital is present (trapped) in the urine as the lipid insoluble ionized form, as this form is unable to diffuse back through the renal tubule epithelium into the blood. The concentration of phenobarbital rises in urine as the water is reabsorbed. Indications: in the PBL case, it is used as an anticonvulsant. It can be used as a sedative- hypnotic. Contraindications: acute intermittent porphyria (a metabolic disease of heme biosynthesis whose clinical symptoms are precipitated by phenobarbital and other barbiturates). 4 IIIR Unit- EPOM – B Course Microbiology Week 2 summary Ali Sultan Adverse effects: dose related toxicity inherent to the pharmacologic effects of phenobarbital: over sedation, coma, respiratory arrest. Sedative effects and potential for respiratory arrest will be additive with other CNC depressants – i.e. alcohol, benzodiazepines, opiates. Dose Modifications: as dose is increased patient will become sedated, so the dose must be carefully monitored for outpatient use as an anticonvulsant. Drug Interactions: barbiturates are inducers (increase the transcriptional activation and amounts) of several CYP enzymes, including the one most commonly involved in metabolizing drugs: CYP3A4. CYP enzyme induction increases the rates of metabolism of drugs metabolized by those enzymes. Thus, CYP induction by barbiturates leads to decreased effectiveness of the barbiturates (this is called dispositional tolerance, and it should be distinguished from cellular tolerance to be discussed later in the course), and to decreased effectiveness of other drugs metabolized by the induced CYPs. Some drugs for which the CYP induction by barbiturates can have clinical consequences include steroids (oral contraceptives – as will enhance metabolism and thereby reduce effectiveness of the contraceptive) and Vitamin D. Ceftriaxone: Brand name: (Rocephin): Pharmacologic effect: blocks cell wall synthesis of many Gram positive and some gram-negative organisms. 3rd generation cephalosporin, a class of drugs particularly useful for treatment against beta lactamase producing bacteria. With the increased resistance to ampicillin, ceftriaxone has become a drug of choice for the treatment of H. influenzae meningitis. Compared to first and second generation cephalosporins it is active against a greater number of gram positive and negative cocci and exhibits increased resistance to beta lactamase producing bacteria. Those characteristics combined with its lipid solubility and facility in crossing the blood brain barrier, contribute to its utility for treatment of H. influenza meningitis. Like other members of its class, it is ineffective against gram positive enterobacteria and should not be used for such enterococcal infections. Pharmacokinetics: lipid solubility allows passage through CNS. Usually given IV (not orally). It is not available for oral treatment and must be given intravenously. It is NOT available for oral administration and is given IV or IM and has a half-life of about 7 to 8 hours making it feasible to administer once a day. Approximately 50% is excreted unchanged. It is mainly eliminated mainly by biliary excretion. Dose adjustments are required only in anephric patients as >50% of the drug is renally excreted unchanged. Indications: infection with susceptible organisms; meningitis. Contraindications: prior anaphylactic reaction to penicillin or beta lactams. Side effects: the main side effect of concern is allergic reactions. Although ceftriaxone is a different molecule from penicillin and has less of a propensity to cause anaphylaxis, (5 to 10% 5 IIIR Unit- EPOM – B Course Microbiology Week 2 summary Ali Sultan cross allergenicity with penicillins) it should not be given to anyone who has had an anaphylactic reaction to penicillin. Another potential concern is the development of thrombophlebitis at the site of injection. Toxicity: allergic reactions. Dose Modifications: no need to modify dose except in patients with very severe renal impairment (reduction of function by 80% or more). Drug Interactions: none of note. Ampicillin/amoxicillin: Pharmacologic effect: as for other penicillins theses antibiotics by targeting the peptidoglycan component of the cell wall and are most effective against Gram-positive bacteria; however, they are so-called “extended spectrum” penicillins, and the added amino group allows them to penetrate the lipid bilayer of some Gram-negative bacteria. Pharmacokinetics: oral or IV; Half-life ~