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Bài giảng dành cho sinh viên y khoa, bác sĩ đa khoa, sau đại học. ĐH Y Dược TP Hồ Chí Minh. ĐỊNH NGHĨA , CƠ CHẾ TÁC ĐỘNG VÀ PHÂN LOẠI KHÁNG SINH, PHỔ TÁC ĐỘNG CỦA KHÁNG SINH, LỰA CHỌN KHÁNG SINH ĐIỀU TRỊ VIÊM PHỔI, THỜI GIAN ĐIỀU TRỊ
ANTIBIOTIC FOR PNEUMONIA PGS.TS.BS PHAN HUU NGUYET DIEM Definition of Antibiotics An Antibiotic is a compound or substance that kills or slows down the growth of bacteria Accordingly, many antibacterial compounds are classified on the basis of chemical/biosynthetic origin into natural, semisynthetic, and synthetic Another classification system is based on biological activity:bactericidal agents kill bacteria, and bacteriostatic agents slow down or stall bacterial growth Classification of Antibiotics Mechanism of Action Inhibitors of Cell Wall Synthesis Beta Lactam Antibiotics Penicillins Cephalosporins Carbapenems Monobactams Penicillines a group of antibiotics derived from Penicillium fungi Inhibits bacterial cell wall synthesis by binding and inactivating proteins (penicillin binding proteins) present in the bacterial cell wall Poor CSF penetration, but can occur if there is menengial inflammation Renal excretion Side effects: hypersensitivity, nephritis, neruotoxicity, platelet dysfunction Penicillines Penicillin G, Penicillin V, Procain PNC, Extencilline Gram positive cocci & rods • • • • • Gram positive anaerobes • • • • Streptococcus Grp A & B Streptococcus viridans Enterococcus Listeria monocytogenes Actinomyces Peptostreptococcus Clostridium tetani Clostridium perfringens Clostridium botulinum Gram negative cocci • Neisseria meningitidis • Pasteurella multocida Spirochetes • Treponema pallidum • Leptospirosis Penicillines Classification of pneumonia (WHO) Children aged 2–59 months: Non-severe pneumonia is diagnosed in a child with cough or difficulty breathing accompanied by tachypnea Severe or very severe pneumonia (lower chest indrawing or central cyanosis), stridor when calm, or IMCI-defined danger signs (inability to drink or breastfeed, convulsions, persistent vomiting, lethargy, or unconsciousness) Children aged less than months with pneumonia have, by definition, severe pneumonia Use of these criteria identifies 80% of children with pneumonia who need antimicrobial therapy Indicators for admission to hospital WHO: severe or very severe pneumonia Uptodate (2010) Most infants < months A child of any age whose family cannot provide appropriate care and assure compliance with the therapeutic Hypoxemia (Sp0 < 92%) Dehydration, or inability to hydration orally and feed in an infant Moderate to severe respiratory distress: RR >70 breaths/min in infants 50 breaths/min in older children, difficulty breathing, apnea, grunting Toxic appearance Underlying conditions: cardiopulmonary disease, metabolic disorder, immunocompromised host) Presence of complications (eg, effusion/empyema) Failure of outpatient therapy (worsening or no response in 24 to 72 hours) COMMUNITY ACQUIRED PNEUMONIA Community-acquired pneumonia is defined as an acute infection of the pulmonary parenchyma in a patient who has acquired the infection in the community (Likely organisms: Strep pneumoniae, or atypical organisms, e.g Mycoplasma pneumoniae, rarely Staph aureus or T.B.) HOSPITAL ACQUIRED (NOSOCOMIAL) PNEUMONIA Hospital-acquired pneumonia (or nosocomial pneumonia) is defined as infection that was not present or incubating at the time of admission to the hospital (pneumonia developing >48 hours from admission to the hospital) (Likely organisms depend on the clinical situation, ranging from Strep pneumoniae, to multiresistant Gram negative bacilli or positive cocci) Outpatient treatment of CAP (WHO recommendations) First-line treatment: amoxicillin is 50 mg/kg per day in two divided doses for a 3-day treatment course in areas with low HIV prevalence, and days in areas of high HIV prevalence In some situations, such as where local evidence clearly indicates infrequent resistance, co-trimoxazole (8 mg/kg trimethoprim in two divided doses) may be an acceptable alternative Outpatient treatment of CAP (WHO recommendations) Treatment failure is defined as the development of lower chest-wall indrawing, central cyanosis, stridor while calm, or IMCI-defi ned danger signs at any time during achild’s illness or a persistently raised respiratory rate at 72 h (48 h in an area of high HIV prevalence) Causes: Wrong diagnosis, Host failure, Complication, Non-susceptible pathogen Outpatient treatment of CAP (WHO recommendations) High-dose amoxicillin with clavulanic acid (80–90 mg/kg per day amoxicillin) for second-line A 5-day treatment course should be prescribed For children over years of age, an aff ordable macrolide or azalide (eg, 50 mg/kg erythromycin in four divided doses for days) may be added to the existing regimen for a 5-day or 7-day treatment course Children failing first-line treatment with cotrimoxazole, the recommendation is to switch to a 5-day course of amoxicillin (50 mg/kg) Outpatient treatment of CAP (UpToDate 2010) to months: Infants with CAP who are febrile or hypoxemic should be admitted to the hospital In afebrile infants with CAP, the most likely bacterial pathogen is C.trachomatis • Azithromycin (20 mg/kg once daily for three days) • Erythromycin (50 mg/kg per day divided every six hours for 14 days) Outpatient treatment of CAP (UpToDate 2010) months to years Viral pneumonia — Viral etiologies predominate Bacterial pneumonia — Streptococcus pneumoniae is the most frequent cause of "typical" bacterial pneumonia in children of all ages M pneumonia and C pneumonia- less common causes of pneumonia, but should be considered in children who fail to improve after 24 to 48 hours of amoxicillin therapy, at which time a macrolide could be added or substituted Outpatient treatment of CAP (UpToDate 2010) Children ≥ years: Amoxicilline 80 to 100 mg/kg per day by mouth in three divided doses (maximum dose to g/day) for to 10 days Non-type hypersensitivity reactions to penicillin: cefdinir (14 mg/kg per day in one or two divided doses; maximum dose 600 mg per day) Type hypersensitivity reactions to penicillin: clindamycin or a macrolide if local resistant rates are high for both of these agents, linezolid may be preferable Outpatient treatment of CAP (UpToDate 2010) Children(30 ≥ 5toyears: Clindamycin 40 mg/kg per day, divided every six to eight hours; maximum to g/day) Erythromycin (30 to 50 mg/kg per day divided every six hours; maximum dose g/day as base, 3.2 g/day as ethyl succinate), or Clarithromycin (15 mg/kg per day divided every 12 hours; maximum dose g/day), or Azithromycin (10 mg/kg administered once on day one [maximum dose 500 mg] followed by mg/kg once daily on days two to five [maximum dose 250 mg/day]), or Linezolid (10 mg/kg every hours for children