Gram Negative Bacteria (1) Pharm D Program (2023/2024) PDF

Pharm D Program (2023/2024) 19 July 2024 www.su.edu.eg 1  Pharm PharmDDProgram Program (2023/2024) (2023/2024)...

Pharm D Program (2023/2024) 19 July 2024 www.su.edu.eg 1  Pharm PharmDDProgram Program (2023/2024) (2023/2024) (PM 704) Lecture No. (5) Gram Negative Bacteria (1) By Professor Yasser El Mohammadi 19 July 2024 www.su.edu.eg 2  Pharm PharmDDProgram Program (2023/2024) (2023/2024) Lecture’s Aim To help the student to get a detailed knowledge about the most virulent and prevalent Gram negative bacteria and their corresponding diseases all over the world. 19 July 2024 www.su.edu.eg 3  Pharm PharmDDProgram Program (2023/2024) (2023/2024) Lecture’s Competencies To enable the student to 1- Discover the most important Gram negative bacteria and to describe their main characteristics. 2- Know the most dangerous & prevalent Gram negative bacterial diseases and how to treat or prevent these diseases. 19 July 2024 www.su.edu.eg 4  Pharm PharmDDProgram Program (2023/2024) (2023/2024) Lecture’s Contents - Gram Negative Cocci Neisseria - Gram Negative Bacilli 1) Escherichia coli 2) Klebsiella 3) Salmonella 4) Shigella 5) Proteus 19 July 2024 www.su.edu.eg 5 Gram Negative Cocci  Neisseria Neisseriae are highly fastidious (require more nutrient supplements to survive) gram –ve diplococci (kidney shape). Species of medical importance: 1. Neisseria gonorrhoeae (Gonococcus): causing gonorrhoea. 2. Neisseria meningitidis (Meningococcus): causing meningitis. 3. Neisseria (Moraxella) catarrhalis: commensal of nasopharynx & mouth. Neisseria meningitidis  1- Neisseria gonorrhoeae (Gonococcus) Epidemiology Gonorrhoea is the most common sexually transmitted disease in the world. New born infants may acquire eye infections (conjunctivitis) from their mothers during delivery which may lead to blindness. Pathogenesis A- Virulence factors 1- Fimbriae: antiphagocytic & facilitate adherence to epithelial cells of urethra & to cervix. 2- IgA protease: facilitates adherence by destroying the secretory IgA which blocks the attachment of the m.o. to epithelial cells of urethra. B- Infections The infection is asymptomatic (sub-clinical) in 30-60% of females & 5-25% of males. a- In male: - Pain burn sensation during urination. - Suppurative urethritis: leading to thick purulent discharge. - Inflammation may extend to other male genital organs such as prostate & testicles resulting in sterility. b- In female: - Suppurative urethritis causing dysuria & vaginal discharge. - Inflammation may extend to other female genital organs such as fallopian tubes causing fibrosis that results in their closure causing sterility. c- In neonates - Eye conjunctivitis known as “Ophthalmia neonatorum” accompanied by mucopurulent discharge which may lead to blindness. Treatment Penicillin is the antibiotic of choice. Resistant strains are treated with ceftriaxone (……….)  2- Neisseria meningitidis (Meningococcus) Causes epidemic cerebrospinal meningitis. Epidemiology Transmitted by inhalation of respiratory droplets. Pathogenesis A- Virulence factors 1- Polysaccharide capsule: Antiphagocytic. The most important virulence factor & many serotypes are classified. 2- Fimbriae: antiphagocytic & facilitate adherence to epithelial cells of nasopharynx. 3- IgA protease: facilitates adherence by destroying the secretory IgA which blocks the attachment of the m.o. to epithelial cells of nasopharynx. B- Infections N. meningitidis inhabits the mucosal surface of nasopharynx from where they reach the brain meninges via blood stream causing bacterial meningitis. Characteristic symptoms: 1- Exudative nasopharyngitis 2- Meningococcemia: This form of bacteremia is the most serious form of the disease; life- threatening with high mortality. Characterized by - Fever. - Disseminated skin hemorrhages leading to widespread purpuric lesions. - Intense vascular congestion & formation of purulent exudates over the brain surface. Purpuric skin lesions (Meningococcemia) Lumbar puncture  Prevention & Control Sulphadiazine (oral or nasal drops) or rifampin. Polyvalent capsular polysaccharide vaccine. Treatment Most strains are sensitive to penicillin & third generation cephalosporins such as ……………… Gram Negative Bacilli  Gram negative rods Source or site of infection Genus 1- Enteric tract Escherichia & Salmonella Shigella, Vibrio & Helicobacter, Klebsiella, Enterobacter, Serratia & Proteus ______________________ 2- Respiratory tract Haemophilus, Bordetella ______________________ & Legionella 3- Animal source Yersinia, Pasteurella, Brucella & Francisella  Enterobacteriaceae Lactose fermenters Non-lactose fermenters (Coliforms) Escherichia, Klebsiella Salmonella, Shigella Citrobacter, Enterobacter Proteus, Yersinia  Characteristics of the Enterobacteriaceae family 1- Facultative anaerobic or aerobic rods inhabiting the intestine. 2- Some enterobacteria are normal flora while others are pathogenic 3- All ferment glucose. 4- All are oxidase negative 5- Reduce nitrate into nitrite 6- Primary classification depends on lactose fermentation. 7- Further classification depends upon biochemical reactions, serological reactions and DNA homology. 8- Transmission: by fecal-oral route. Coliforms are very important source of nosocomial infections.  1- Escherichia coli Normal inhabitant of the human intestine Some strains are able to cause diseases. Pathogenesis A- Virulence factors 1- Pili: facilitate adhesion 2- K or capsular polysaccharide antigen: interfere with phagocytosis. 3- Exotoxins B- Infections 1- Intestinal diseases i) Enterotoxigenic E. coli (ETEC) Gastroenteritis ‫نزلة معوية‬ Affects small intestine causing traveler’s diarrhea & infant diarrhea that may lead to dehydration. Diarrhoea is caused by toxins that induce loss of sodium & loss of potassium. ii) Enteropathogenic E. coli (EPEC) Causes diarrhea due to adherence of the m.o. to the small intestine mucosa. Gastroenteritis iii) Enteroinvasive E. coli (EIEC) Infection is due to due to invasion of the large intestinal mucosa causing fever, cramps, watery diarrhea followed by development of dysentery with scant, bloody stools. iv) Enterohemorrhagic E. coli (EHEC) Affects large intestine, causing hemorrhagic colitis. There is cramps, watery diarrhea, followed by bloody diarrhea without pus in stool. Usually results from uncooked meat or hamburger in fast food restaurants (hamburger disease). 2- Urinary tract infection The most common agent causing urinary tract infection especially in females where the infection is chronic & usually resulting in premature delivery due to endotoxins. Kidney invasion (pyelonephritis) could lead to renal failure. 3- Nosocomial infections  Laboratory diagnosis (Practical ----) Specimen according to the site of infection (stool, urine, ……). Treatment Ampicillin & tetracycline are used for intestinal infections. Nalidixic & nitrofurantoin are used for urinary tract infection. In case of severe diarrhea, replace electrolytes and fluids.  2) Klebsiella Kl. pneumoniae Causes lobar pneumonia with multiple cavitation. Kl. aerogenes Normal inhabitant of intestine, but may cause urinary tract infection.  3) Salmonella S. typhi, S. S. enteritidis paratyphi A, B &C 1- Cause typhoid fever (enteric fever) 1- Cause food poisoning & paratyphoid. 2- Penetrate the intestinal mucosa 2- Do not penetrate mucosa 3- Detected in blood, urine and stool 3- Detected in stool only  Salmonella typhi Typhoid fever (Enteric fever) ‫التيفوئيد او الحمى المعوية‬ Salmonella typhi causes typhoid fever. Sal. paratyphi causes a milder form called paratyphoid fever. Transmission Ingestion of food or drink contaminated by case or carrier stools (feces-flies-fingers-food: 4F), specially poultry, or undercooked or raw egg foods. The M.O. resists freezing and could be transmitted even by ice cream.  Pathogenesis The M.O. multiplies in Peyer’s patches, then passes to the blood through the lymphatics resulting in bacteraemia that persists for one week. In the second week the M.O. passes to different organs including again the Peyer’s patches of the intestine causing ulcers also to gall bladder, liver & kidneys. Characteristic symptoms: Fever, headache, loss of appetite, malaise, delirium and tender abdomen with dough like touch. Complications of the disease include diarrhea, intestinal hemorrhage and perforation.  Typhoid septicemia - occurs 10-14 days – lasts 7 days gall bladder –shedding, weeks acute phase, gastroenteritis gastrointenteritis  Chronic carrier is due to presence of the m.o. in the gall bladder and recurrence in such carriers usually every year may require removal of the gall bladder. Laboratory diagnosis Specimen: Blood (1st week), urine (2nd week), & stool (3rd week). Microscopical characters: (Practical). Culture characteristics: (Practical). Serological reactions: (Practical). Treatment Chloramphenicol is the drug of choice. Ciprofloxacin or ceftriaxone is used for resistant strains.  4) Shigella Bacillary Dysentery ‫الدوسنتاريا الباسيلية‬ Transmission 4F transmission, usually in low hygiene communities. Pathogenesis Pathogenesis is mainly due to invasion of the colon mucosa by means of an exotoxin causing ulceration & necrosis of the intestinal (colon) mucosa known as “ulcerative colitis”. Characterized by: abdominal cramps & tenesmus, bloody diarrhea with abundant pus and fever. Ulcerative Colitis  Laboratory diagnosis Specimen: Stool or rectal swab. Microscopical characters: (Practical). Culture characteristics: (Practical). Treatment - Ampicillin or tetracycline - Trimethoprim + sulfamethoxazole.  5) Proteus Species of medical importance: 1- Proteus vulgaris & Proteus mirabilis caused urinary tract infection. They produce urease enzyme, which decomposes urea into ammonia, that increases the pH of urine, thus facilitating calcium stone formation. Laboratory diagnosis (Practical). Specimen: Urine or stool. Treatment: Sensitivity test is recommended because of high resistance.  Pharm PharmDDProgram Program (2023/2024) (2023/2024) Lecture’s References Review of Medical Microbiology and Immunology. By Warren Levinson - 10th Edition (2008). Publisher: McGraw Hill - Lange. 19 July 2024 www.su.edu.eg 45