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Antibiotics mbg Antibiotics mbg Presentation Transcript

  • M.AM.ATPMC Antibiotics Medical background Microbiology, Infections, and Antibiotic Therapy
  • M.AM.ATPMC 1-Microbiology Microbiology, Infections, and Antibiotic Therapy
  • M.A tabuk tabuk Shapes of Bacteria ▪ Coccus ➢ Chain = Streptoccus ➢ Cluster = Staphylococcus ▪ Bacillus ➢ Chain = Streptobacillus ▪ Coccobacillus ▪ Vibrio = curved ▪ Spirochete
  • M.A tabuk tabuk Bacterial Structures ▪ Flagella ▪ Capsule ▪ Plasma Membrane ▪ Cytoplasm ▪ Cell Wall ➢ Lipopolysaccharides ➢ Teichoic Acids ➢ Inclusions ▪ Spores
  • M.A Cytoplasm ▪ 80% Water {20% Salts-Proteins) ▪ DNA is circular, ➢ More efficient; grows quicker ➢ Mutations allow adaptation to environment quicker ▪ Plasmids; extra circular DNA ➢ Antibiotic Resistance ▪ No organelles (Mitochondria, Golgi, etc.)
  • M.A Cell Membrane ▪ Bilayer Phospholipid ▪ Water can penetrate ✹Flexible ✹Not strong, ruptures easily
  • M.A Cell Wall ▪ Peptido-glycan Polymer (amino acids + sugars) ▪ Unique to bacteria ▪ Sugars; ➢ N- acetylglucosamine ➢ N- acetylmuramic acid
  • M.A tabuk tabuk Gm+ve Bacteria
  • M.A Gm-ve Bacteria
  • M.A MEMBRANE STRUCTURE Gm+ve Gm-ve
  • M.A 1-Gram Positive Cocci Staphylococcus ▪ S. aureus, S. epidermidis, S. saprophyticus ▪ S. aureus
  • M.A Streptococcus ▪ S. viridans ➢oral flora ➢infective endocarditis
  • M.A S. pyogenes ▪ Group A, beta hemolytic strep ▪ pharyngitis, Tonsillitis , cellulitis ▪ rheumatic fever o fever o migrating polyarthritis o carditis o immunologic cross reactivity ▪ acute glomerulonephritis o edema, hypertension, hematuria o antigen-antibody complex deposition
  • M.A S. pneumoniae
  • M.A 2-Gram Negative Cocci ▪ Neisseria ➢ meningitidis ➢ gonorrhea ▪ Moraxella catarrhalis
  • M.A 3-Gram Positive Bacilli ▪ Clostridium ▪ Bacillus ▪ Corynebacterium ▪ Listeria ▪ Actinomyces ▪ Nocardia
  • M.A 4-Gram Negative Bacilli ▪ Facultative Anaerobes ➢ Respiratory • Haemophilus • Bordetella • Legionella ➢ Zoonotic • Yersinia • Francisella • Pastuerella ➢ Enteric • Klebsiella • Serratia • Proteus • Enterobacter ▪ Strict Aerobes ➢ Pseudomonas ▪ Anaerobes ➢ Bacteroides
  • M.A Enterobacteriaceae
  • M.A H. influenzae
  • M.A Legionella ▪ Community and Nosocomial pneumonia ▪ contaminated water sources
  • M.A Pseudomonas
  • M.A tabuk tabuk 5-Anaerobic Bacteria ▪ Bacteroides ▪ Fusobacterium ▪ Peptostreptococcus ▪ Actinomyces ▪ Prevotella
  • M.A 6-Other Bacteria ● Atypical Bacteria • Mycoplasma pneumoniae or hominis • Chlamydia pneumoniae or trachomatis ● Spirochetes • Treponema pallidum
  • M.A Bacteria by Site of Infection Mouth Peptococcus Peptostreptococcus Actinomyces Skin/Soft Tissue S. aureus S. pyogenes S. epidermidis Pasteurella Bone and Joint S. aureus S. epidermidis Streptococci N. gonorrhoeae Gram- negative Bacilli Abdomen E. coli, Proteus Klebsiella Enterococcus Bacteroides sp. Urinary Tract E. coli, Proteus Klebsiella Enterococcus Staph saprophyticus Upper Respiratory S. pneumoniae H. influenzae M. catarrhalis S. pyogenes Lower Respiratory Community S. pneumoniae H. influenzae K. pneumoniae Legionella pneumophila Mycoplasma, Chlamydia Lower Respiratory Hospital K. pneumoniae P. aeruginosaEnterobacter sp. Serratia sp. S. aureus Meningitis S. pneumoniae N. meningitidis H. influenza Group B Strep E. coli Listeria
  • M.A
  • M.A Normal Bacterial Flora
  • M.A Normal Bacterial Flora ▪ All body surfaces possess a rich normal bacterial flora, especially the mouth, nose, gingiva, large intestine, skin ➢ This can be a nuisance in that o it can contaminate specimens o it can cause disease ➢ This is beneficial in that o it can protect against infection by preventing pathogens colonising epithelial surfaces (colonisation resistance) o removal of the normal flora with antibiotics can cause superinfection, usually with resistant microbes
  • M.A Bacterial Growth ▪ Binary Fission = Exponential Growth ▪ Four Phases of Growth
  • M.AM.ATPMC Pathogenesis Principles ofBacterial Infections
  • M.A Microbes and humans Very few microbes arealways pathogenic Many microbes are potentially pathogenic Most microbes arenever pathogenic
  • M.A Bacterial Virulence ▪ There are many different ways to define a “virulence factor”… ▪ needed to colonise and/or damage tissues ➢ “Biochemical evidence of damaging potential ▪ distinguishes pathogen from commensal ✹ Virulence as a process is ✹ MULTIFACTORIAL ✹ A bacterial army, like a human army, needs more than just its firearms to enter and secure enemy territory… ✹ MULTIDIMENSIONAL ✹ A programme of events organised in time and space
  • M.A Bacterial acquiring virulence genes ▪ Bacteria have three ways of exchanging DNA ➢ Transformation o cells take up new DNA ➢ Transduction o phages carry DNA ➢ Conjugation o cells mate through specialised appendages -Environment -Scavenge nutrients -Stick -Avoid immune system -Damage host tissues *Endotoxin *Membrane-Damaging Exotoxins -Spread
  • M.AM.ATPMC 2-Pathology Microbiology, Infections, and Antibiotic Therapy
  • M.A Respiratory Tract Infections (R.T.I.s)
  • M.A
  • M.A Upper Respiratory Tract Infections (U.R.T.I.s)
  • M.A Acute Rhinitis (Coryza, Common Cold) ▪ Acute inflammation of the nasal mucosa is accompanied by markedly increased mucous secretion (catarrhal inflammation). ▪ The watery nasal discharge may be accompanied by sore throat due to pharyngeal involvement, fever, and muscle aches. ▪ Acute infectious rhinitis (coryza) is almost/ always the result of viral infection and is one of the most common infections of humans. ▪ It is caused by many different viruses, commonly rhinoviruses, influenza viruses, myxoviruses, paramyxoviruses, and adenoviruses
  • M.A Allergic Rhinitis ▪ Type I hypersensitivity is also a common cause of acute rhinitis (hay fever). ▪ Susceptible patients are affected by a variety of allergens, most commonly pollens and dust. ▪ Patients who suffer from allergic rhinitis commonly have a positive family history and an increased frequency of developing other atopic diseases such as bronchial asthma and atopic dermatitis.
  • M.AM.ATPMC Tonsillopharyngitis
  • M.A Definitions ▪ Tonsillitis: inflammation of pharyngeal tonsils. ▪ Tonsillopharyngitis: inflammation extending from tonsils to the adenoids and lingual tonsils. ▪ Recurrent tonsillitis: 7 episodes in 1 year, 5 infections in 2 consecutive years, or 3 infections each year for 3 years consecutively. ▪ Chronic tonsillitis: chronic sore throat, halitosis, tonsillitis, and persistent tender cervical nodes for greater than 4 weeks. ▪ quinsy: Greek term used for inflammation of throat and tonsils, historically used for peritonsillar abscess
  • M.A Epidemiology ▪ Most cases occur in school-age children. ▪ Uncommon in the first 2 years of life. ▪ 5-7 URIs per child per year. ▪ GAS (Group A-Betahymolytic Streptococci) is found in 35% of children with pharyngitis. ▪ Causes of Tonsillopharyngitis • Beta hemolytic streptococcal infection — 22 %. • Mycoplasma pneumoniae — 9.4 %. • Chlamydia species strain — 8.4 %. • Viruses — 25.5 %. Huovinen, et al 1995
  • M.A CLINICAL DIAGNOSIS The "classic" presentation of GAS tonsillopharyngitis is a sore throat associated with fever, tonsillopharyngeal erythema and exudate, swollen and tender anterior cervical adenopathy, and an elevated white blood cell (WBC) count without rhinorrhea or cough. However, even when this constellation of clinical symptoms is present, the likelihood of GAS infection does not exceed 60 to 70 percent in children, and 20 to 30 percent in adults.
  • M.A Is it truly Group A beta hemolytic Streptoccal tonsillopharyngitis? ▪ From many studies, it would appear that the presence or absence of a GAS pharyngitis cannot be accurately diagnosed with clinical examination alone in most patients. ▪ It is somewhat easier to identify a subset of children (approximately 20 percent of cases) and adults (approximately 67 percent of cases) who are unlikely to have GAS. ▪ These patients have sore throats with accompanying rhinorrhea, cough, and hoarseness. Fever is often absent. They have mild tonsillopharyngeal erythema without exudate, and slight or no cervical lymphadenitis.
  • M.A Why antibiotics ▪ Treatment of GABHS pharyngitis is important ▪ To prevent complications of infection, ➢particularly rheumatic fever ➢suppurative complications ▪ To speed recovery ▪ To prevent spread of the infection
  • M.A
  • M.A Recommendations on the Management of Acute and Chronic Tonsillitis ▪ Adequate supportive care. ▪ Use of analgesics, oral anesthetics, and antiseptics. ▪ Antibiotics: 1-in the AHA (American Heart Association) guidelines, prevention of rheumatic fever as a poststreptococcal complication depends on eradication of GABHS bacteria from the pharynx 2-prevention of rheumatic fever and other nonsuppurative complications of GABHS pharyngitis still occurs when antibacterial therapy is postponed by as many as 9 days after the onset of pharyngitis symptoms
  • M.AM.ATPMC SINUSITIS
  • M.A Anatomy of Paranasal Sinuses
  • M.A What are the sinuses? ▪ The sinuses are hollow air-filled sacs lined by mucous membrane. The ethmoid and maxillary sinuses are present at birth. The frontal sinus develops during the 2nd year and the sphenoid sinus develops during the 3rd year. ▪ Sinuses have small orifices (ostia) which open into recesses (meati) of the nasal cavities. ▪ Meati are covered by turbinates (conchae). ▪ Turbinates consist of bony shelves surrounded by erectile soft tissue. ▪ There are 3 turbinates and 3 meati in each nasal cavity (superior, middle, and inferior). ▪ The funtion of sinuses is to reduce the weight of the skull and adjust temperature of the air
  • M.A Sinusitis ▪ Inflammation of paranasal sinuses
  • M.A What is sinusitis? ▪ An acute inflammatory process involving one or more of the paranasal sinuses. ▪ A complication of 5%-10% of URIs in children. ▪ Persistence of URI symptoms >10 days without improvement. ▪ Maxillary and ethmoid sinuses are most frequently involved.
  • M.A Predisposing Factors ▪ Allergies, nasal deformities, cystic fibrosis, nasal polyps, and HIV infection. ▪ Cold weather. ▪ High pollen counts. ▪ Day care attendance. ▪ Smoking in the home. ▪ Reinfection from siblings.
  • M.A Acute or Chronic Sinusitis? ▪ Acute Sinusitis – respiratory symptoms last longer than 10 days but less than 30 days. ▪ Subacute sinusitis – respiratory symptoms persist longer than 30 days without improvement. ▪ Chronic sinusitis – respiratory symptoms last longer than 120 days.
  • M.A Etiology of Sinusitis 70% of bacterial sinusitis is caused by: ▪ Streptococcus pneumoniae 30%. ▪ Haemophilus influenzae 20%. ▪ Moraxella catarrhalis 20%. Other causative organisms are: ▪ Staphylococcus aureus. ▪ Streptococcus pyogenes, ▪ Gram-negative bacilli . ▪ Respiratory viruses .
  • M.A Subjective Symptoms of Sinusitis ▪ History of URI or allergic rhinitis. ▪ History of pressure change. ▪ Pressure, pain, or tenderness over sinuses. ▪ Increased pain in the morning, subsiding in the afternoon. ▪ Malaise. ▪ Low-grade temperature. ▪ Persistent nasal discharge, often purulent. ▪ Postnasal drip. ▪ Cough, worsens at night. ▪ Mouthing breathing, snoring. ▪ History of previous episodes of sinusitis. ▪ Sore throat, bad breath. ▪ Headache.
  • M.A Pharmacological Plan of Care ▪ Codeine – for severe pain. ▪ Corticosteroid or Nasal decongestant spray – 2 sprays in each nostril every 12 hours for children over 6 years of age. ▪ Antimicrobials-treat for 10-14 days, depending upon severity
  • M.A OTC Medications ▪ Acetaminophen or ibuprofen to relieve pain. ▪ Decongestants. ▪ Antihistamines. ▪ Nasal saline
  • M.AM.ATPMC OTITIS MEDIA
  • M.A
  • M.A OTITIS MEDIA ▪ Definition: Presence of a middle ear infection. ▪ Acute Otitis Media: occurrence of bacterial infection within the middle ear cavity. ▪ Otitis Media with Effusion: presence of nonpurulent fluid within the middle ear cavity. ▪ OM is the second most common clinical problem in childhood after upper respiratory infection.
  • M.A EPIDEMIOLOGY ▪ Peak incidence in the first two years of life (esp. 6-12 months). ▪ Boys are more affected than girls. ▪ 50% of children 1 yr of age will have at least 1 episode. ▪ 1/3 of children will have 3 or more infections by age 3. ▪ 90% of children will have at least one infection by age 6. ▪ Occurs more frequently in the winter months
  • M.A MICROBES AT FAULT!!! ▪ Streptococcus pneumoniae, ▪ Haemophilus influenzae(non-typeable). ▪ Moraxella catarrhalis. ▪ Group A Streptococcus. ▪ Staph aureus. ▪ Pseudomonas aeruginosa
  • M.A Classification of Otitis Media ▪ Acute Otitis Media: presents with fever, otalgia, and hearing loss. ▪ Otitis Media with Effusion: evidence of middle ear effusion on pneumatic otoscopy. ▪ Recurrent Otitis Media: inability to clear middle ear effusions. ▪ Chronic Serous Otitis Media: presents as ‘fullness in the ear’, tinnitus, or another acute disease.
  • M.A PATHOGENESIS ▪ This problem mainly deals with eustacian tube dysfunction. ▪ Otitis Media usually follows an URI in which there is edema of the eustacian tube, leading to blockage. ▪ Stasis of these middle ear secretions lead to infection and irritation. ▪ Other factors: allergic rhinitis, nasal polyps, adenoidal hypertrophy.
  • M.A SIGNS & SYMPTOMS ▪ Neonates/Infants: change in behavior, irritability, tugging at ears, decreased appetite, vomiting. ▪ Children(2-4): otalgia, fever, noises in ears, cannot hear properly, changes in personality. ▪ Children (>4): complain of ear pain, changes in personality.
  • M.A
  • M.A TREATMENT ▪ Antibiotic. ▪ Symptomatic treatment
  • M.AM.ATPMC Lower Respiratory Tract Infections (L.R.T.I.s)
  • M.A Bronchitis
  • M.A Acute exacerbations of chronic bronchitis (A.E.C.B) ▪ Chronic bronchitis: cough and sputum production most days for >3 months in two consecutive years. ▪ AECB - Some combination of worsening dyspnea, increased sputum volume, and/or increase in sputum purulence. ▪ Etiology: Nontypable H. influenzae 50-60%, M. catarrhalis 15-20%, S. pneumoniae 15-20%, Atypicals 5-10%. ▪ Most cases of CB are due to tobacco use (85-90%); also environmental pollutants, genetic factors. ▪ 12 million cases of chronic bronchitis (CB) per year in the U.S. - Most common category of chronic obstructive pulmonary disease (COPtent to which specific bacterial pathogens explain exacerbations is controversial.
  • M.A tabuk tabuk Pneumonia
  • M.A Pneumonia ▪ 6th leading cause of death in U.S.A. ▪ In USA , about 3 million cases per year; > 500,000 hospital admissions. ▪ About 50% of cases and the majority of deaths are due to bacteria. ▪ Precise diagnosis is usually desirable but difficult to obtain
  • M.A
  • M.A tabuk tabuk Etiology ▪ There are two factors involved in the formation of pneumonia , including pathogens and host defenses.
  • M.A Pneumonia ▪ Streptococcus pneumoniae the most common cause of community-acquired pneumonia requiring hospitalization. ▪ Haemophilus influenzae and Moraxella catarrhalis are increasing in frequency. ▪ Legionella species and Chlamydia pneumoniae have emerged. ▪ Pneumocystis carinii (HIV disease)
  • M.A Pneumonia: pathogenesis ▪ Endogenous vs. exogenous (inhalation). ▪ Bronchogenous vs. lymphohematogenous. ▪ “Pulmonary clearance”: mucociliary blanket, alveolar macrophages. ▪ Factors that impair pulmonary clearance: viral URI; smoking; alcohol; uremia; bronchial obstruction; 100% oxygen; others
  • M.A Pneumonia: pathophysiology ▪ Hypoxemia due to ventilation/perfusion mismatching. ▪ Hyperdynamic circulation with increased cardiac output. ▪ “Toxic cardiomyopathy”. ▪ Increased oxygen demands. ▪ Decreased lung compliance; increased work of breathing
  • M.A “Typical” versus “atypical” pneumonia ▪ “Typical” (virulent bacteria): abrupt onset; productive cough with purulent sputum; pleuritic chest pain; impressive physical findings; leukocytosis or leukopenia . ▪ “Atypical” (viral, Mycoplasma pneumoniae, others): gradual onset, nonproductive cough; substernal chest pain; unimpressive physical exam; white blood count normal
  • M.A tabuk tabuk Typical Vs. Atypical pneumonia
  • M.A Classic pneumococcal pneumonia ▪ Antecedent upper respiratory infection. ▪ Sudden onset with single violent chill, then fever. ▪ Pleuritic chest pain. ▪ Signs of lobar consolidation on exam. ▪ If untreated, terminates gradually by “lysis” or suddenly by “crisis”
  • M.A Atypical pneumococcal pneumonia ▪ Caught early: signs of consolidation may be absent. ▪ Elderly: fever, classic history may be absent. ▪ COPD: Physical findings are distorted. ▪ Ethanolism: blunted history; prostration, leukopenia. ▪ Epilepsy: lack of history; fever and tachycardia may be attributed to seizures; anaerobes may co-exist. ▪ Recurrent pneumonia: In same area, suggests obstruction or bronchiectasis
  • M.A tabuk tabuk Group A streptococcal pneumonia ▪ Rare, except during influenza epidemics. ▪ Large empyema (“pus in the chest”) is characteristic
  • M.A Hemophilus influenzae pneumonia ▪ 2% to 18% of community-acquired pneumonias; increasing in adults. ▪ Predispose: underlying lung disease, alcoholism, recent URI, advanced age. ▪ Often a patchy segmental pneumonia or bronchopneumonia. ▪ Virtually-diagnostic Gram’s stain: small, pleomorphic gram-negative coccobacilli.
  • M.A Moraxella catarrhalis pneumonia ▪ Moraxilla Catarrhalis ,Neisseria catarrhalis; Branhamella catarrhalis. ▪ A large gram-negative diplococcus. ▪ Causes pneumonia and bronchitis especially in persons with chronic lung disease. ▪ Often a patchy bronchopneumonia
  • M.A Mycoplasma pneumoniae pneumonia ▪ The classic “primary atypical pneumonia”. ▪ Typically occurs in younger adults, often the parents of young children. ▪ Subtle presentation. ▪ Favors lower lobes. ▪ Pleural effusion may occur (up to 20%)
  • M.A Chlamydia pneumoniae pneumonia ▪ Accounts for perhaps 6% to 10% of community- acquired pneumonias. ▪ C. pneumoniae more commonly causes pharyngitis and hoarseness. ▪ Bronchitis is often insidious. ▪ Pneumonia usually mild and localized but difficult to eradicate
  • M.A Legionella pneumophila pneumonia ▪ Up to 23% of community-acquired pneumonias but with wide geographic distribution. ▪ L. pneumophila is not part of the normal flora; a true inhalation disorder. ▪ XR: patchy or nodular infiltrates that may progress rapidly; up to 50% are bilateral. ▪ Relative bradycardia in 65^. ▪ Neurologic findings in 26%. ▪ Gram’s stain may show purulence without a predominant microorganism. ▪ Laboratory: may have hyponatremia; elevations of AST (SGOT), alkaline phosphatase, and bilirubin; proteinuria, hematuria, and renal failure.
  • M.AM.ATPMC Urinary Tract Infections
  • M.A
  • M.A Urinary Tract Infection Prevalence ■ Community-dwelling elders – 25% Swart, Soler & Holman, 2004 ■ Long-term care elders 25-50% of women (chronically bacteriuric) 15-40% of men Juthani-Mehta et al., 2005 ■ Marked increases in women & men after age 65 Wagenlehner, Naber & Weidner, 2005 }
  • M.A Overview of UTI ▪ 7 million office visits yearly. ▪ 1 million hospitalizations. ▪ About 2/3rds of patients are women; 40% to 50% of women have UTI at some point during their lives. ▪ Important complications of pregnancy, diabetes mellitus, polycystic disease, renal transplantation, conditions that impede urine flow (structural and neurologic) .
  • M.A tabuk tabuk Overview of UTI by age and sex
  • M.A Urinary Tract Infection Women: Presence of at least 100,000 colony- forming units (cfu)/mL in a pure culture of voided clean-catch urine Men: Presence of just 1,000 cfu/mL indicates urinary tract infection *Some labs do not routinely identify & determine the sensitivity of organisms for specimens with <10,000 cfu/mL. May have to special request. Swart, Soler & Holman, 2004
  • M.A
  • M.A Urinary Tract Infection ■ Urinary tract infection—most common source of bacteremia, a dangerous systemic infection in long- term care facilities ■ Bacteremia—40 times more likely to occur in catheterized than non-catheterized residents ■ Bacteremia leads to significant morbidity and mortality in the vulnerable elderly Nicolle, 2005
  • M.A Frequency of significant bacteriuria ▪ After one bladder catheterization: 2% ▪ Medical outpatients: 5% ▪ Pregnancy at term: 10% ▪ Hypertensive patients: 14% ▪ Diabetes mellitus: 20% ▪ Women with cystocoele (bladder dropping): 23%
  • M.A Complicated vs Uncomplicated UTI ▪ UTI’s in elderly men are always considered complicated ▪ UTI’s in women are complicated when: ➢ Recurrent UTI ➢ Secondary to structural abnormalities ➢ Catheters ➢ Stones ➢ Urinary retention ➢ Abscess formation or urosepsis ▪ Primary diagnostic and treatment focus in research studies have been related to the elderly female population Swart, Soler & Holman, 2004
  • M.A Complicated vs Uncomplicated UTI Recurrent UTI’s — culture-confirmed UTI’s * >3 in 1 year or * > 2 in 6 months ▪ Relapse UTI — occurs within 2 weeks of Rx of an earlier UTI same pathogen ▪ Re-infection UTI — occurs >4 weeks after earlier UTI different pathogen Swart, Soler & Holman, 2004
  • M.A Causative Pathogens UTI in Women z Escherichia coli—gram (-) etiologic agent in ~ 80% of all UTI’s z Research indicates primary source of microbial invasion is retrograde colonization by intestinal pathogens z Other factors influencing colonization: vaginal pH, urethral length, capacity of bacteria to adhere to urothelium Polymicromial bacteriuria z Contamination most frequent cause of multiple microorganisms z 25-33% in LTCF’s (Long Term Care Facilities) may be polymicrobic due to fistulas, urinary retention, infected stones, or catheters Age/Type Specific Pathogens z Younger patients, rare in elderly—Staphylcoccus, saprophyticus (gram pos.) – 10-15% z Elderly diabetics ◆ Klebsiella species (gram neg.) most common z LTCF elderly ◆ E. coli ~ 30% ◆ Proteus species (part of host flori in GI tract) ~ 30% ◆ Staphylcoccus aureus, Klebsiella, Pseudomonas (gram neg.) and Enterococcus (gram pos.) ~ 40% CTCF’s=long-term care facilities
  • M.A
  • M.A UTI Symptoms 1-Burning Sensation when you come to the end of urination. 2-Constant feeling to urinate. 3-Cloudy and Foul smelling Odor. 4-Fever,loss of appetite, nausea and vomiting.
  • M.A Prostatitis ▪ Relapsing acute urinary tract infection in men caused by the same bacterial species often suggests chronic prostatitis with periodic spill- over into the bladder. ▪ Symptoms: pelvic “heaviness,” rectal or perineal pain, urinary hesitancy, dribbling (Urge to urinate), and burning. ▪ A risk of catheterization
  • M.A Treatment Plan ▪ AB Rx for at least 10 days for institutionalized elderly, as short-term therapy may not be as effective. ▪ Ten-14 days, if indicated, for complicated UTI. (recommended for males) Evercare, 2004 ▪ Conventional regimen of 7-10 days duration is usually recommended. Wagenlehner et al. 2005
  • M.AM.ATPMC Pelvic Inflammatory Disease (PID)
  • M.A Etiology ▪ Neisseria gonorrhoeae common cause of PID ▪ 85% of infection → sexually active female of reproductive age ▪ 15% of infection occur after procedures that break cervical mucous barrier ▪ Bacteria culture direct from tubal fluid common : N. gonorrhoeae, C. trachomatis, endogenous aerobic, anaerobic, genital mycoplasma spp.
  • M.A ▪ C. trachomatis ➢ produce mild form of salpingitis ➢ slow growth (48-72 hr) ➢ intracellular organism ➢ insidious onset ➢ remain in tubes for months/years after initial colonization of upper genital tract ➢ more severe tubes involvement ▪ N. gonorrhoeae ➢ gram –ve diplococcus ➢ rapid growth (20-40 min) ➢ rapid & intense inflammatory response ➢ 2 major sequelae (Result) o infertility & ectopic pregnancy, strong asso. with prior Chalamydia infection PID
  • M.A Risk factors ▪ Age of 1st intercourse. ▪ Frequency of intercourse. ▪ Number of sexual partners. ▪ Marital status ; 33% → Nulliparous (is the medical term for a woman who has never given birth to a viable, or live, infant) . ▪ Increase risk ➢ IUD user (multifilament string) ➢ surgical procedure ➢ previous acute PID ▪ Reinfection → untreated male partners 80% ▪ Decrease risk - barrier method
  • M.A Diagnosis ▪ Common clinical manifestation. ➢ lower abdominal pain 90%. ➢ cervical motion tenderness. ➢ adnexal tenderness. ➢ Fever. ➢ cervical discharge. ➢ Leukocytosis.
  • M.A PID
  • M.A Squeal ▪ Infertility ➢ ¼ of pt have acute salpingitis. ➢ occur 20%. ➢ infertility rate increase direct with number of episodes of acute pelvic infection. ▪ Ectopic pregnancy. ➢ increase 6-10 fold. ➢ 50% occur in fallopian tubes. (previous salpingitis) ➢ mechanism ; interfere ovum transport entrapment of ovum. ▪ Chronic pelvic pain: ➢ 4 times higher after acute salpingitis. ➢ caused by hydrosalpinx, adhesion around ovaries. ➢ should undergo laparoscope → R/o other disease. ▪ Mortality ➢ acute PID 1% ➢ rupture TOA (Tubo-ovarian abscess)5-10%
  • M.A Treatment ▪ Therapeutic goal: ➢ eliminate acute infection & symptoms. ➢ prevent long-term sequelae. ➢ Empirical ABx cover wide range of bacteria. ▪ Rx male partners & education for prevention reinfection. ▪ Rx male partners → regimens for uncomplicated gonorrhoeae & chlamydial infection.
  • M.AM.ATPMC Skin and Soft Tissue Infection (SSTI)
  • M.A
  • M.A Skin - Definitions ▪ Vesicles: ➢ small, fluid-filled lesions in the epidermis (eg. chicken pox) ▪ Bullae: ➢ larger, fluid-filled lesions in the epidermis ▪ Macules: ➢ flat, reddish lesion from inflammatory Infiltrate ▪ Papules: ➢ raised lesion which, when it contains pus, is called pustule
  • M.A -S. pyogenes. It is a painful, bright red, shiny lesion with a raised, sharply demarcated, advancing edge. It is most common on the legs or face and often spreads across the nose to involve both cheeks (the `butterfly-wing' rash. -There is much systemic upset with high fever and rigors and a leucocytosis is common. Erysipelas is treated with penicillin, given parenterally in the more severe cases. Erysipelas
  • M.A tabuk tabuk Furunculosis(boils) ▪ A furuncle or boil is an acute round, tender, circumscribed, perifollicular staphylococcal inflammation, which generally tends to suppurate.
  • M.A Carbuncle ▪ A carbuncle is a circumscribed inflammation caused usually by Staph. Aureus complicating certain diseases such as diabetes or other conditions that lower the body resistance. ▪ Carbuncles are composed of furuncles joined together in the subcutaneous area. Suppuration is more deeply seated than in the furuncles.
  • M.A tabuk tabuk Folliculitis ▪ Folliculitis is bacterial infection of skin appendages that originates within the hair follicles. ▪ In infants and young children, the scalp is the commonest site involved while in adults any hairy area may be affected.
  • M.A tabuk tabuk Impetigo ▪ Impetigo is a contagious superficial bacterial skin infection most common in children caused by staphylococci and to a lesser extent by streptococci pyogenes
  • M.A Cellulitis Features: Red Swollen Warm to touch No areas of pus Painful Tender Cellulitis
  • M.A Cellulitis
  • M.A Cellulitis Describe the features that make this cellulitis
  • M.A Abscess Features: Cellulitis present Swollen Soft center, feels like fluid underneath Painful Tender Cellulitis Absces s
  • M.A Necrotizing fasciitis
  • M.A What is MRSA? ▪ It is Staphylococcus aureus, ▪ Which is a particular bacteria that is the most common cause of skin infection in injectors as well as non- injectors. ▪ Methicillin Resistant Staphylococcus aureus. ▪ MRSA is just Staph aureus that is resistant to Methicillin type antibiotics AND. ▪ It has picked up some new genes that make it more aggressive in skin, and more likely to cause skin infection than “regular old” Staph aureus. ▪ It now accounts for half the skin infections in injecting drug users
  • M.A Acne Vulgaris
  • M.A Acne vulgaris: overview Introduction: Definition: Multi-factorial disease characterized by abnormalities in sebum production, follicular desquamation, bacterial proliferation and inflammation. Prevalence: ✓ 85% adolescents experience it ✓ Prevalence of comedones (lesions) in adolescents approaches 100% ✓ affects 8% of 25 - 34y yr olds, and 3% of 35-44yr olds
  • M.A Pathogenesis: Acne vulgaris is a disease of pilosebaceous follicles. Factors: ▪ Retention hyperkeratosis. ▪ Increased sebum production. ▪ Propionibacterium acnes within the follicle. ▪ Inflammation
  • M.A Initial pathogenesis (reason unknown): follicular hyperkeratinization proliferation + decreased desquamation of keratinocytes hyperkeratotic plug (microcomedone)
  • M.A Pathogenesis Sebaceous glands enlarge Sebum production increases Growth medium for P. Acnes plugs provide anaerobic Lipid-rich environment
  • M.A Pathogenesis Bacteria thrive Inflammation results Chemotactic factors attract neutrophils Depending on conditions Non-inflammatory open/closed comedones Inflammatory papule/ pustule/nodule
  • M.A
  • M.A Closed comedones (whiteheads) ▪ Closed comedo (a whitehead): Accumulation of sebum converts a microcomedo into this.
  • M.A Open comedo (blackhead) ▪ open comedo (a blackhead): when follicular orifice is opened + distended. Melanin + packed keratinocytes + oxidized lipids → dark colour
  • M.A Cysts ▪ Cysts: when follicles rupture into surrounding tissues, resulting in papule/pustule/nodule.
  • M.A Pustular
  • M.A Acne Treatment ▪ Topical Keratolytic ▪ Topical & systemic antibiotics ▪ Combination of both ▪ Combination rx more effective than mono in increased inflammatory lesions. ▪ Hormonal treatment ▪ Lazer Therapy
  • M.A Bone Infections
  • M.A
  • M.A Bone Infections ▪ Septic arthritis ➢ infection of joint spaces ➢ hematogenous or contiguous ➢ S. aureus, Streptococcus spp., Gram-negative bacilli. ▪ Osteomyelitis ➢ infection of the bone ➢ hematogenous or contiguous ➢ S. aureus, S. pyogenes, H. influenzae, Gram-negative bacilli
  • M.A Diabetic Foot Infection ▪ Cellulitis>Deep soft tissue infection>Osteomyelitis ▪ Risk factors: ➢ vascular disease (macro and micro). ➢ peripheral neuropathy. ➢ poor foot care.
  • M.A Diabetic Foot Infection ▪ Organisms: ➢skin organisms: S. aureus, β-hemolytic strep, diphtheroids ➢Gram-negative bacilli (E. coli, K. pneumoniae, Pseudomonas spp.) ➢Anaerobes.
  • M.A Dental Infections
  • M.A
  • M.A
  • M.A GINGIVITIS Gingivitis, also generally called gum disease or periodontal disease, describes the events that begin with bacterial growth in your mouth and may end – if not properly treated – with tooth loss due to destruction of the tissue that surrounds your teeth. Actually, gingivitis and periodontitis are two distinct stages of gum disease.
  • M.A GINGIVITIS ❑Gingivitis usually precedes periodontitis. ❑Bacteria in plaque build up and cause the gums to become inflamed (red and swollen) and often easily bleed during tooth brushing. ❑The teeth are still firmly planted in their sockets. ❑No irreversible bone or other tissue damage has occurred at this stage.
  • M.A GINGIVITIS ❑In periodontitis, the inner layer of the gum and bone pull away from the teeth and form pockets. ❑These small spaces between teeth and gums collect debris and can become infected. ❑The body's immune system fights the bacteria as the plaque spreads and grows below the gum line. ❑Toxins or poisons – produced by the bacteria in plaque as well as the body's "good" enzymes involved in fighting infections – start to break down the bone and connective tissue that hold teeth in place. ❑As the disease progresses, the pockets deepen and more gum tissue and bone are destroyed. ❑When this happens, teeth are no longer anchored in place, they become looser, and tooth loss occurs. Gum disease, in fact, is the leading cause of tooth loss in adults.
  • M.A SYMPTOMS OF PERIODONTAL DISEASE ❑May progress painlessly, producing few obvious signs, even in the late stages of the disease. ❑Symptoms include: •Bleeding gums during and after tooth brushing •Red, swollen, or tender gums •Persistent bad breath or bad taste in the mouth •Receding gums •Formation of deep pockets between teeth and gums •Loose or shifting teeth •Changes in the way teeth fit together upon biting down, or in the fit of partial dentures. ❑In some people, gum disease may affect only certain teeth, such as the molars.
  • M.A ❑The goals of periodontal treatment are to promote reattachment of healthy gums to teeth; reduce swelling, the depth of pockets, and the risk of infection; and to stop disease progression. ❑Treatment options depend on the stage of disease, how you may have responded to earlier treatments, and your overall health. ❑Options range from nonsurgical therapies that control bacterial growth to surgery to restore supportive tissues. TTT OF PERIODONTAL DISEASE
  • M.A PREVENTION OF GINGIVITIS Proper plaque control: - Professional cleanings at least twice a year - Daily brushing and flossing. - Stop smoking (7 TIMES HIGHER RISK). Decrease your stress. Maintain a well-balanced diet. NB: ❑Despite following good oral hygiene practices and making other healthy lifestyle choices, The American Academy of Periodontology says that up to 30% of the Americans may be genetically susceptible to gum disease. ❑And those who are genetically predisposed may be up to six times more likely to develop some form of gum disease.
  • M.A TTT OF GINGIVITIS ❑Non-surgical treatments of gum disease include: •Professional dental cleaning to remove the plaque and tartar. •Scaling and root planing. ❑Surgical treatments of gum disease include: •Flap surgery/pocket reduction surgery. •Soft tissue grafts. •Guided tissue regeneration. •Bone surgery. NB/ Surgery is needed when the tissue around your teeth is unhealthy and cannot be repaired with nonsurgical options.
  • M.A Medications Used to Treat Gum Disease ❑Antibiotic treatments can be used either in combination with surgery and other therapies, or alone, to reduce or temporarily eliminate the bacteria associated with periodontal disease or suppress the destruction of the tooth's attachment to the bone. ❑Antiseptic mouth washes. ❑Toothpaste that contains fluoride and an antibiotic to reduce plaque and gingivitis. TTT OF GINGIVITIS CONT..
  • M.A STOMATITIS Generalized inflammation of the oral mucosa of many possible etiologies STOMATITIS – APHTHOUS ULCER
  • M.A STOMATITIS Predominant age: •Herpetic-primary infections - children •Hand-foot-and-mouth disease - children •Vincent's stomatitis - teenagers and young adults •Behçet's disease - young adults •Herpangina - children Male = Female CAUSES: - Allergy - foods, drugs, contact (some erythema multiforme) - Vitamin deficiency - riboflavin (angular stomatitis) - Viral - herpes simplex I and II (herpetic stomatitis), Coxsackie A (herpangina and hand-foot-and-mouth disease) - Smoking (nicotinic stomatitis) - Hormonal (possibly recurrent ulcerative stomatitis) - Uncertain - Bacterial (scarlatina) - Uremic (uremic/nephritic) - Dentures
  • M.A GLOSSITIS Glossitis is an abnormality of the tongue that results from inflammation
  • M.A GLOSSITIS - CAUSES ❑Bacterial ❑viral infections (including oral herpes simplex) ❑Mechanical irritation, trauma or injury from burn ❑Irritants such as tobacco, alcohol, hot foods, or spices ❑Allergic (toothpaste, mouthwash, breath fresheners, etc) ❑Systemic causes (Iron deficiency anaemia, pernicious anaemia, other B vitamin deficiencies, etc) ❑Inherited.
  • M.A GLOSSITIS – SYMPTOMS / SIGNS ❑Smooth appearance to the tongue ❑Tongue color usually dark "beefy" red •Pale, if caused by pernicious anaemia •Fiery red, if caused by deficiency of B vitamins ❑Sore and tender tongue ❑Difficulty with chewing, swallowing, or speaking
  • M.A GLOSSITIS - PREVENTION ❑Good oral hygiene (thorough tooth brushing and flossing and regular professional cleaning and examination) may be helpful to prevent these disorders. ❑Minimize irritants or injury in the mouth when possible. ❑Avoid excessive use of any food or substance that irritates the mouth or tongue.
  • M.A GLOSSITIS - TTT ❑Treatment is to reduce inflammation. Treatment usually does not require hospitalization unless tongue swelling is severe. ❑Good oral hygiene is necessary, including thorough tooth brushing at least twice a day, and flossing at least daily. ❑Corticosteroids such as prednisone may be given to reduce the inflammation of glossitis. ❑For mild cases, topical applications (such as a prednisone mouth rinse that is not swallowed) may be recommended to avoid the side effects of swallowed or injected corticosteroids. ❑Antibiotics, antifungal medications, or other antimicrobials may be prescribed if the cause of glossitis is an infection. ❑Anemia and nutritional deficiencies must be treated, often by dietary changes or other supplements. ❑Avoid irritants (such as hot or spicy foods, alcohol, and tobacco) to minimize the discomfort.
  • M.AM.ATPMC 3-Antibiotics Medical Background Microbiology, Infections, and Antibiotic Therapy
  • M.A History of Antibiotics Time line of events 1900 2000 1928, Penicillin discovered 1932, Sulfonamides discovered 1940’s: Penicillin becomes commercially available and Cephalosporins are synthesized 1952, Erythromycin discovered 1956, Vancomycin introduced 1962, Quinolones discovered 1980’s, Fluorinated Quinolones available More potent Less toxic Changes to increase activity Linezolid becomes available
  • M.A Antibiotic Therapy Choice of Antibiotic: ▪ Identify infecting organism ▪ Evaluate drug sensitivity ▪ Target site of infection ▪ Drug safety/side effect profile ▪ Patient factors ▪ Cost
  • M.A Classification of Antibiotics ▪ Bacteriostatic ▪ Bactericidal
  • M.A Mechanism of Action
  • M.A Inhibitors of Cell Wall Synthesis
  • M.A Mode Of Action Of Beta-Lactams
  • M.A tabuk tabuk Beta Lactam Antibiotics ▪ Penicillins ▪ Cephalosporins ▪ Carbapenems ▪ Monobactams
  • M.A Beta-Lactam Structure
  • M.A Penicllins ▪ Derived from the fungus Penicillium. ▪ Therapeutic concentration in most tissues. ▪ Poor CSF (Cerebrospinal Fluid) penetration. ▪ Renal excretion. ▪ Side effects: hypersensitivity, nephritis, neruotoxicity, platelet dysfunction
  • M.A ALL β-lactams • Mechanism of Action ➢interfere with cell wall synthesis by binding to penicillin-binding proteins (PBPs) which are located in bacterial cell walls. ➢inhibition of PBPs leads to inhibition of peptidoglycan synthesis. ➢They are bactericidal.
  • M.A ALL β-lactams • Mechanisms of Resistance ➢production of beta-lactamase enzymes • most important and most common. • hydrolyzes beta-lactam ring causing inactivation. ➢alteration in PBPs leading to decreased binding affinity. ➢alteration of outer membrane leading to decreased penetration.
  • M.A Antimicrobial Spectrum of Activity ▪ General list of bacteria that are killed or inhibited by the antibiotic: ➢ are established during early clinical trials of the antibiotic. ➢ local, regional and national susceptibility patterns of each bacteria should be evaluated; differences in antibiotic activity may exist. ▪ Individualized susceptibilities should be performed on each bacteria if possible.
  • M.A Natural Penicillins ▪ Penicillin G, Penicillin V
  • M.A Antistaphylococcal Penicillins ▪ Methicillin ▪ Nafcillin ▪ Oxacillin ▪ Dicloxacillin
  • M.A Aminopenicillins ▪ Amoxicillin +/- clavulanate ▪ Ampicillin +/- sulbactam
  • M.A Antipseudomonal Penicillins ▪ Carbenicillin ▪ Ticarcillin +/- clavulanate ▪ Piperacillin +/- tazobactam
  • M.A tabuk tabuk Cephalosporins ➢ Structurally similar to penicillins. ➢ Therapeutic concentration in many tissues, 3rd and 4th generation into CSF. ➢ Renal Excretion. ➢ Side Effects • allergy • disulfiram-like effect • anti-Vitamin K
  • M.A Classification and Spectrum of Activity of Cephalosporins • Divided into 4 major groups called “Generations” • Are divided into Generations based on ➢Antimicrobial activity. ➢Resistance to beta-lactamase
  • M.A First Generation Cephalosporins Best activity against gram-positive aerobes, with limited activity against a few gram-negative aerobes Gram-positive Gram- negative meth-susc S. aureus E. coli pen-susc S. pneumoniae K. pneumoniae Group streptococci P. mirabilis viridans streptococci
  • M.A Second Generation Cephalosporins • Also includes some cephamycins and carbacephems. • In general, slightly less active against gram- positive aerobes, but more active against gram- negative aerobes. • Several second generation agents have activity against anaerobes.
  • M.A Second Generation Cephalosporins Spectrum of Activity Gram-positive Gram- negative meth-susc S. aureus E. coli pen-susc S. pneumoniae K. pneumoniae Group streptococci P. mirabilis viridans streptococci H. influenzae M. catarrhalis
  • M.A Second Generation Cephalosporins Spectrum of Activity The cephamycins (cefoxitin, cefotetan, and cefmetazole) are the only 2nd generation cephalosporins that have activity against anaerobes Anaerobes Bacteroides fragilis group
  • M.A Third Generation Cephalosporins Spectrum of Activity • In general, are even less active against gram-positive aerobes, but have greater activity against gram-negative aerobes • Ceftriaxone and cefotaxime have the best activity against gram-positive aerobes, including pen- resistant S. pneumoniae • Several agents are strong inducers of extended spectrum beta-lactamases
  • M.A Third Generation Cephalosporins Spectrum of Activity Gram-negative aerobes E. coli, K. pneumoniae, P. mirabilis H. influenzae, M. catarrhalis, N. gonorrhoeae (including beta-lactamase producing); N. meningitidis Citrobacter sp., Enterobacter sp., Acinetobacter sp. Morganella morganii, Serratia marcescens, Providencia Pseudomonas aeruginosa (ceftazidime and cefoperazone)
  • M.A Fourth Generation Cephalosporins !!! • 4th generation cephalosporins for 2 reasons ➢Extended spectrum of activity • gram-positives: similar to ceftriaxone • gram-negatives: similar to ceftazidime, including Pseudomonas aeruginosa; also covers beta-lactamase producing Enterobacter sp. ➢Stability against β-lactamases; poor inducer of extended-spectrum β -lactamases. • Only cefepime is currently available
  • M.A Cephalosporens
  • M.A Generations of Cephalosporins
  • M.A tabuk tabuk Monobactams ▪ Aztreonam ➢ single beta lactam ring. ➢ narrow spectrum: gram- negative aerobes. • Enterobacteriacea. • Pseudomonas. ➢ given IV/IM. ➢ renal excretion. ➢ little cross-reactivity with other beta lactams. ➢ side effects: phlebitis, rash, elevated LFT’s (Liver function tests).
  • M.A tabuk tabuk Carbapenems ▪ Meropenem/Imipenem ➢ broad spectrum. ➢ active against MRSA. ➢ given IV. ➢ penetrates CSF. ➢ renal metabolism and excretion. ➢ addition of cilastin. ➢ side effects: GI upset, eosinophilia, neutropenia, lowering of seizure threshold.
  • M.A β-LactamsAdverse Effects • Hypersensitivity – 3 to 10 % ➢Higher incidence with parenteral administration or procaine formulation. ➢Mild to severe allergic reactions – rash to anaphylaxis and death. ➢Antibodies produced against metabolic by- products or penicillin itself ➢Cross-reactivity exists among all penicillins and even other β-lactams. ➢Desensitization is possible.
  • M.A β-Lactams Adverse Effects • Neurologic – especially with penicillins and carbapenems (imipenem) ➢Especially in patients receiving high doses in the presence of renal insufficiency. ➢Irritability, confusion, seizures. • Hematologic ➢Leukopenia, neutropenia, thrombocytopenia – prolonged therapy (> 2 weeks).
  • M.A β-Lactams Adverse Effects • Gastrointestinal ➢Increased LFTs, nausea, vomiting, diarrhea, pseudomembranous colitis (C. difficile diarrhea). • Interstitial Nephritis: ➢Cellular infiltration in renal tubules (Type IV hypersensitivity reaction – characterized by abrupt increase in serum creatinine; can lead to renal failure. ➢Especially with methicillin or nafcillin.
  • M.A Vancomycin ▪ Tricyclic glycopeptide. ▪ Inhibits synthesis of phospholipids and cross-linking of peptidoglycans. ▪ Activity against gram-positive organisms. ▪ Useful for beta lactam resistant infections. ▪ Widely distributed, penetrates CSF. ▪ Renal elimination, follows creatinine cl. ▪ Side effects: phlebitis, red man syndrome, ototoxicity, nephrotoxicity.
  • M.A tabuk tabuk Protein Synthesis Inhibitors ▪ Human Ribosome ➢ 80S • 40S • 60S ▪ Bacterial Ribosome ➢ 70S • 30S • 50S
  • M.A Protein Synthesis Inhibitors ▪ Mostly bacteriostatic. ▪ Selectivity due to differences in prokaryotic and eukaryotic ribosomes. ▪ Some toxicity – eukaryotic 70S ribosomes.
  • M.A Review of Elongation of Protein Synthesis G TP AP T u G TP T u G D PT s T s T u + G D P T s Pi P ATetracycline AP G G TP G G D P + Pi G G D P AP + Erythromycin Fusidic Acid Chloramphenicol
  • M.A Tetracyclines ▪ Isolated from Streptomyces aureofaciens. ▪ Reversibly bind 30S ribosomal subunit. ▪ Penetrate sinus mucosa, saliva and tears. ▪ Metabolized in liver-->excreted in bile--> reabsorbed-- >eliminated in urine. ▪ Side effects: GI upset, hepatotoxicity, photosensitivity, bony deposition. ▪ Contraindicated in pregnant or breast feeding women, children under 8 y/o
  • M.A Tetracyclines
  • M.A Aminoglycosides ▪ Derived from Streptomyces and Micormonospora. ▪ Irreversible binding to 30S subunit. ▪ Actively transported into bacterial cells. ▪ Variable tissue penetration, unreliable CSF levels. ▪ Concentrate within perilymph. ▪ Renal elimination. ▪ Nephrotoxicity, ototoxicity, neurotoxicity.
  • M.A Aminoglycosides
  • M.A Aminoglycosides Pharmacokinetics • Absorption - poorly absorbed from G.I. tract. • Distribution: ➢ primarily in extracellular fluid volume; are widely distributed into body fluids but NOT the CSF. ➢ distribute poorly into adipose tissue, use Lean Body Weight (LBW) for dosing. • Elimination: ➢ eliminated unchanged by the kidney via glomerular filtration; 85-95% of dose. ➢ elimination half-life dependent on renal fxn • normal renal function - 2.5 to 4 hours • impaired renal function - prolonged
  • M.A Aminoglycosides Adverse Effects Nephrotoxicity: ➢ nonoliguric azotemia due to proximal tubule damage; increase in BUN (Blood Urine Nitrogen) and serum Cr; reversible if caught early. ➢ risk factors: prolonged high troughs, long duration of therapy (> 2 weeks), underlying renal dysfunction, elderly, other nephrotoxins. Ototoxicity: ➢ 8th cranial nerve damage - vestibular and auditory toxicity; irreversible. ➢ vestibular: dizziness, vertigo, ataxia – S, G, T ➢ auditory: tinnitus, decreased hearing – A, N, G ➢ risk factors: same as for nephrotoxicity
  • M.A Spectinomycin (bacteriostatic) ▪ Mode of action - Spectinomycin reversibly interferes with m-RNA interaction with the 30S ribosome. It is structurally similar to the aminoglycosides but does not cause misreading of mRNA. ▪ Spectrum of activity - Used in the treatment of penicillin- resistant Neisseria gonorrhoeae ▪ Resistance - Rare in Neisseria gonorrhoeae
  • M.A Macrolides ▪ Macrocyclic lactone structure. ▪ Irreversible binding to 50S subunit. ▪ Therapeutic concentrations in oropharyngeal and respiratory secretions. ▪ No CSF penetration. ▪ Metabolized in liver, excreted in feces and urine. ▪ Side effects: GI upset, ototoxicity, hepatotoxicity
  • M.A Erythromycin
  • M.A Alternate Macrolides ▪ Clarithromycin ▪ Azithromycin
  • M.A Macrolides Mechanisms of Resistance ➢ Active efflux (accounts for 80%) – mef gene encodes for an efflux pump which pumps the macrolide out of the cell away from the ribosome; confers low level resistance to macrolides. ➢ Altered target sites encoded by the erm gene which alters the macrolide binding site on the ribosome; confers high level resistance to all macrolides, clindamycin and Synercid . ➢ Cross-resistance occurs between all macrolides.
  • M.A Macrolides Pharmacokinetics Absorption ➢ Erythromycin – variable absorption food may decrease the absorption : • Base: destroyed by gastric acid; enteric coated. • Esters and ester salts: more acid stable. ➢ Clarithromycin – acid stable and well-absorbed regardless of presence of food. ➢ Azithromycin –acid stable; food decreases absorption of capsules
  • M.A Macrolides Pharmacokinetics Distribution ➢ Extensive tissue and cellular distribution – clarithromycin and azithromycin with extensive penetration. ➢ Minimal CSF penetration. Elimination: ➢ Clarithromycin is the only macrolide partially eliminated by the kidney (18% of parent and all metabolites); requires dose adjustment when CrCl < 30 ml/min. ➢ Hepatically eliminated: ALL. ➢ NONE of the macrolides are removed during hemodialysis!. ➢ Variable elimination half-lives (1.4 hours for erythro; 3 to 7 hours for clarithro; 68 hours for azithro).
  • M.A Macrolides Adverse Effects • Gastrointestinal – up to 33 %. ➢ Nausea, vomiting, diarrhea, dyspepsia ➢ Most common with erythro; less with new agents • Cholestatic hepatitis – rare. ➢ > 1 to 2 weeks of erythromycin estolate • Thrombophlebitis – IV Erythro and Azithro: ➢ Dilution of dose; slow administration • Other: ototoxicity (high dose erythro in patients with RI); QTc prolongation; allergy.
  • M.A Macrolides Drug Interactions Erythromycin and Clarithromycin ONLY– are inhibitors of cytochrome p450 system in the liver; may increase concentrations of: Theophylline. Digoxin, Disopyramide. Carbamazepine. Valproic acid. Cyclosporine. Terfenadine, Astemizole. Phenytoin. Cisapride. Warfarin. Ergot alkaloids.
  • M.A Chloramphenicol ▪ Isolated from Streptomyces. ▪ Reversible binding to 50S subunit. ▪ Broad spectrum of activity. ▪ Indicated for severe anaerobic infections or unresponsive life- threatening infections. ▪ Widely distributed, enters CSF. ▪ Metabolized in liver (inhibits P-450), eliminated in urine. ▪ Toxicities: reversible anemia, hemolytic anemia, aplastic anemia, gray baby syndrome.
  • M.A Clindamycin ▪ Semisynthetic derivative of Lincomycin. ▪ Irreversible binding to 50S subunit. ▪ Covers anaerobes and gram + aerobes. ▪ Widely useful for head and neck infections. ▪ Penetrates saliva, sputum, pleural fluid, and bone, but not CSF. ▪ Metabolized in liver-->reabsorbed-->eliminated in urine. ▪ Side effects: rash, neutropenia/thrombocytopenia, pseudomembranous colitis.
  • M.A Fusidic acid (bacteriostatic) ▪ Mode of action - Fusidic acid binds to elongation factor G (EF-G) and inhibits release of EF-G from the EF-G/GDP complex. ▪ Spectrum of activity - Gram-positive cocci.
  • M.A tabuk tabuk Inhibitors of Metabolism ▪ Sulfonamides. ▪ Trimethoprim. ▪ Interfere with the production of folic acid coenzymes that are required for purine and pyrimidine synthesis
  • M.A Sulfonamides
  • M.A Trimethoprim ▪ Inhibits dihydrofolate reductase. ▪ 1000x higher affinity for bacterial enzyme than human enzyme. ▪ Similar spectrum and pharmacokinetic profile as sulfas. ▪ Side effects: folate deficiency anemia, leukopenia, granulocytopenia
  • M.A Co-Trimoxazole (TMP/SMX) ▪ Combination gives synergistic antibacterial action
  • M.A Co-Trimoxazole (TMP/SMX)
  • M.A Fluoroquinolones • Novel group of synthetic antibiotics developed in response to growing resistance. • Agents available today are all structural derivatives of nalidixic acid. • The fluorinated quinolones (FQs) represent a major therapeutic advance: ➢ Broad spectrum of activity. ➢ Improved PK properties – excellent bioavailability, tissue penetration, prolonged half-lives. ➢ Overall safety. • Disadvantages: resistance, expensive
  • M.A Topoisomerase Enzymes ▪ Involved in DNA replication, transcription, and recombination. ▪ Targets for anticancer (Topoisomerase I and Topoisomerase II) and antibacterial drugs (DNA Gyrase, Topoisomerase IV)
  • M.A Gyrase ▪ Fluoroquinolones antibiotics target gyrase:
  • M.A The Quinolones ▪ DNA gyrase consist of 2 A subunits and 2 B subunits and is important in uncoiling superhelical DNA into covalently closed DNA circles and reversible joining of DNA circles (catenation and decatenation). ▪ Fluoroquinolone binding to DNA gyrases inhibits the rejoining reactions after breakage of the closed DNA circles. Net result is inhibition of supercoiling. ▪ Fluoroquinolones are bactericidal agents.
  • M.A Quinolones ▪ Inhibit topoisomerases/DNA synthesis: ➢ Trap enzyme-DNA complex after strand breakage. ➢ DNA gyrase (topo III) (gyrA/gyrB): o Primary target in Gram-negatives. ➢ Topoisomerase IV [parC/parE (grlA/grlB in S.aur)] : o Primary target in Gram-positives.
  • M.A Fluoroquinolones Gemifloxacin
  • M.A Fluoroquinolone Classification System (2-12)0 Brand Generic Manufacturer Generation Microbiology General Indications NegGram Nalidixic acid Sanofi-synthelabo 1st Gram Negative but not pseudomonas Uncomplicated UTIs Noroxin Norfloxacin Merck 2nd As above but including pseudomonas. Some gram + including s.aureus. Not strep pneumoniae. Atypical including chlamydia, mycoplasma and legionella. UTIs, Pyelonephritis, STD, Prostatitis, Skin and soft tissue infections Maxaquin Lomefloxacin Searle / Pfizer 2nd Tarivid Ofloxacin Sanofi Aventis 2nd Ciprobay Ciprofloxacin Bayer 2nd Tavanic Levofloxacin Sanofi Aventis 3rd Same as above +expanded gram — including pen sensitive and resistant s. pneumoniae. More so with Tequin and Avelox Acute exacerbations of chronic bronchitis and community acquired pneumoniae Zagam Sparfloxacin Sanofi Aventis 3rd Tequin Gatifloxacin Bristol-Myers Squibb 3rd Avelox Moxifloxacin Bayer 3rd Factive Gemifloxacin LG Life sciences 3rd As other 3rd generation plus activity against gram –ve as 2nd generations+Activity against MDRSP (Multi-Drug Resistant Streptococcus Pneumoniae) Acute exacerbations of chronic bronchitis , community acquired pneumoniae and ABS +UTI,Prostatitis Trovan Trovafloxacin Pfizer 4th Same as above plus broad anaerobic coverage As above except UTIs and pyelonephritis. Plus intra-abdominal infections, PID and nosocomial pneumonia
  • M.A
  • M.A Fluoroquinolones • Mechanism of Action ➢Unique mechanism of action. ➢Inhibit bacterial topoisomerases which are necessary for DNA synthesis: ▪ DNA gyrase – removes excess positive supercoiling in the DNA helix. − Primary target in gram-negative bacteria. ▪ Topoisomerase IV – essential for separation of interlinked daughter DNA molecules − Primary target for many gram-positive bacteria. ➢FQs display concentration-dependent bactericidal activity.
  • M.A Fluoroquinolones • Mechanisms of Resistance: ➢ Altered target sites – chromosomal mutations in genes that code for DNA gyrase or topoisomerase IV • most important and most common. ➢ Altered cell wall permeability – decreased porin expression. ➢ Expression of active efflux – transfers FQs out of cell. ➢ Cross-resistance occurs between FQs.
  • M.A The Available FQs Older FQs ▪ Norfloxacin (Noroxin®) – PO. ▪ Ciprofloxacin (Ciprobay®) – PO, IV. Newer FQs ▪ Levofloxacin (Tavanic®) – PO, IV. ▪ Gatifloxacin (Tequin®) – PO, IV. ▪ Moxifloxacin (Avelox®) – PO, IV. ▪ Gemifloxacin (Factive®) – PO.
  • M.A FQs Spectrum of Activity Gram-positive – older agents with poor activity; newer FQs with enhanced potency : o Methicillin-susceptible Staphylococcus aureus. o Streptococcus pneumoniae (including PRSP). o Group and viridans streptococci – limited activity. o Enterococcus sp. – limited activity.
  • M.A FQs Spectrum of Activity Gram-Negative – all FQs have excellent activity (cipro=levo>gati>moxi): • Enterobacteriaceae – including E. coli, Klebsiella sp, Enterobacter sp, Proteus sp, Salmonella, Shigella, Serratia marcescens, etc. • H. influenzae, M. catarrhalis, Neisseria sp. • Pseudomonas aeruginosa – significant resistance has emerged; ciprofloxacin and levofloxacin with best activity
  • M.A FQs Spectrum of Activity Anaerobes – only trovafloxacin has adequate activity against Bacteroides sp. Atypical Bacteria – all FQs have excellent activity against atypical bacteria including: o Legionella pneumophila o Chlamydia sp. o Mycoplasma sp. o Ureaplasma urealyticum. Other Bacteria – Mycobacterium tuberculosis, Bacillus anthracis
  • M.A Fluoroquinolones Pharmacology • Concentration-dependent bacterial killing – AUC/MIC (AUIC) correlates with efficacy • Absorption ➢ Most FQs have good bioavailability after oral administration ➢ Cmax within 1 to 2 hours; coadministration with food delays the peak concentration • Distribution ➢ Extensive tissue distribution – prostate; liver; lung; skin/soft tissue and bone; urinary tract ➢ Minimal CSF penetration • Elimination – renal and hepatic; not removed by HD
  • M.A FluoroquinolonesAdverse Effects • Gastrointestinal – 5 % ➢ Nausea, vomiting, diarrhea, dyspepsia • Central Nervous System ➢ Headache, agitation, insomnia, dizziness, rarely, hallucinations and seizures (elderly) • Hepatotoxicity ➢ LFT elevation (led to withdrawal of trovafloxacin) • Phototoxicity (uncommon with current FQs) ➢ More common with older FQs (halogen at position 8) • Cardiac ➢ Variable prolongation in QTc interval ➢ Led to withdrawal of grepafloxacin, sparfloxacin
  • M.A Fluoroquinolones Adverse Effects • Articular Damage: ➢ Arthopathy including articular cartilage damage, arthralgias, and joint swelling. ➢ Observed in toxicology studies in immature dogs. ➢ Led to contraindication in pediatric patients and pregnant or breastfeeding women. ➢ Risk versus benefit. • Other adverse reactions: tendon rupture, dysglycemias, hypersensitivity
  • M.A Fluoroquinolones
  • M.A Prophylactic Antibiotics ▪ Cover bacterial flora involved in the surgical field. ▪ Administer within 2 hours before or 3 hours after surgery has begun. ▪ Maintain therapeutic blood level during lengthy procedures. ▪ Continue prophylaxis for the 24 hour period surrounding surgery
  • M.A Topical Antibiotic Prophylaxis ▪ significantly reduce bacterial counts in the oral cavity. ▪ both immediate effect and prolonged effect for approximately 4 hours. ▪ reduce post-op wound infections alone and in combination with parenteral antibiotic therapy
  • M.AM.ATPMC Antibiotic Pressure and Resistance in Bacteria
  • M.A Antibiotic Pressure and Resistance in BacteriaWhy is it important? ▪ Antibiotic resistance has developed in almost all classes of bacteria of pathogenic potential. ▪ Resistance in organisms of low virulence can emerge as important pathogens. ▪ The development of resistant bacteria has driven pharmaceutical research to develop more potent, broad- spectrum antibiotics. ▪ Use of these in turn, has fueled the appearance of bacteria with newer modes of resistance.
  • M.A Antibiotic Pressure and Resistance in BacteriaWhy is it important? ▪ Infections with resistant bacteria occur in health care settings AND the community. ▪ Examples of hospital setting: MDR Gram neg, MRSA, VRE. ▪ Examples of community : MRSA, PRSP, Pcn R Quin R N. gonorrhea, antibiotic resistant Salmonella and Shigella.
  • M.A Antibiotic Resistance
  • M.A Emergence of Antibiotic-Resistant Bacteria Cohen; Science 1992;257:1050 Gram-negative rods Enterococcus sp. N. gonorrhoeae H. influenzae M. catarrhalis S. pneumoniae 1950 1960 1970 1980 1990 S aureus P e n i c i l l i n A m p i c i l l i n 3rd gen Cephalosporins Quinolones
  • M.A Scope of Problem:S. pneumoniae ▪ Most common cause of bactemia, bacterial pneumonia, meningitis, OM, sinusitis in childhood. ▪ Highest rates of invasive pneumococcal disease occur among young children, especially those aged <2 years. ▪ US data: the seven most common serotypes isolated from the blood or CSF of children age <6 years account for 80% of disease . ▪ Antimicrobial resistance is detected most frequently among these same serotypes. ▪ 1998 surveillance data from eight states: these serotypes accounted for 80% of penicillin-nonsusceptible isolates.
  • M.A Antibiotic Pressure and Resistance in BacteriaHow does it happen ? ▪ Bacteria can become resistant as a result of genetic mutations; these can be transferred between bacteria and groups of bacteria. ▪ Under selective pressure of antibiotic exposure, these strains then proliferate.
  • M.A Antibiotic Pressure and Resistance in Bacteria What factors promote their development and spread ? < Alteration of normal flora. < Practices contributing to misuse of antibiotics. < Settings that foster drug resistance. < Failure to follow infection control principles.
  • M.A < Inappropriate specimen selection and collection. < Inappropriate clinical tests. < Failure to use stains/smears. < Failure to use cultures and susceptibility tests. Practices Contributing to Misuse of Antibiotics
  • M.A < Use of antibiotics with no clinical indication (eg, for viral infections). < Use of broad spectrum antibiotics when not indicated. < Inappropriate choice of empiric antibiotics. Inappropriate Antibiotic Use
  • M.A < Inappropriate dose - ineffective concentration of antibiotics at site of infection. < Inappropriate route - ineffective concentration of antibiotics at site of infection. < Inappropriate duration. Inappropriate Drug Regimen
  • M.A Public campaign, physician education, and increased antibiotic cost 25 89 90 91 92 93 94 95 96 0 5 10 15 20 Stephenson, JAMA 1996;275:175 Controlling Pneumococcal Resistance- Iceland %nonsusceptibleS. pneumoniae
  • M.A Controlling Erythromycin Resistance in Group A Streptococci - Finland Seppala, NEJM 1997;337:441 Yea r Erythromycinresistance(%) 87 88 89 90 91 92 93 94 95 96 0 1 2 3 4 5 10 15 20 25 30 Erythromycin resistance Erythromycin consumption
  • M.A Thank you