Infectious diseases for nurse tudent1.pptx

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1. Integrated therapeutics iv (Phar 442) By Ameha Zewudie B- pharm , MSC in clinical pharmacy 1

2. 2 Antimicrobial Regimen Selection

3. Outlines 3 Objectives Introduction Systematic Approach for Selection of Antimicrobials Failure of Antimicrobial Therapy Antimicrobial Use Management

4. Objectives 4 At the end of the class students will be able to: Discuss the systemic approach to select antimicrobials. Identify host and drug factors to be considered during antimicrobials selection. Devise a plan to monitor the efficacy and toxicity of an antimicrobial regimen List reasons for a patient to fail a specific antimicrobial regimen. Explain antimicrobial use management

5. Brain storming questions 5 What is infectious disease? What infectious disease do you know? What are the drugs that we use to treat infectious disease ? How do we select the drugs that we use to treat infectious disease ?

6. Introduction Choosing an antimicrobial agent to treat an infection is far more complicated than matching a drug to a known or suspected pathogen. Follow a systematic approach to select an antimicrobial regimen. Infectious diseases generally are acute, and a delay in antimicrobial therapy can result in serious morbidity or even mortality. Every attempt should be made to obtain specimens for culture and sensitivity testing prior to initiating antibiotics. Empirical antibiotic therapy should be based on knowledge of likely pathogens for the site of infection, information from patient history (e.g., recent hospitalizations, work-related exposure, travel, and pets), and local susceptibility. 6

7. Introduction… 7 Patients with delayed dermatologic reactions (i.e., rash) to penicillin generally can receive cephalosporins. Patients with type I hypersensitivity reactions (i.e., anaphylaxis) to penicillins should not receive cephalosporins. Alternatives to the cephalosporins include aztreonam, quinolones, sulfonamide antibiotics, or vancomycin based on type of coverage indicated. Creatinine clearance should be estimated for every patient who is to receive antibiotics and the antibiotic dose interval adjusted accordingly. Hepatic function should be considered for drugs eliminated through the hepatobiliary system, such as clindamycin, erythromycin, and metronidazole.

8. Introduction… 8 All concomitant drugs and nutritional supplements should be reviewed when an antibiotic is added to a patient’s therapy. Combination antibiotic therapy may be indicated for polymicrobial infections (e.g., intraabdominal, gynecologic infections), to produce synergistic killing (such as β- lactam plus aminoglycoside vsPseudomonas aeruginosa ) to prevent the emergence of resistance. Antibiotics with the narrowest effective spectrum of activity are preferred. Antibiotic route of administration should be evaluated daily. conversion from IV to oral therapy should be attempted as signs of infection improve for patients with functioning GI tracts general exceptions are endocarditis and CNS infections.

9. Introduction… 9 Patients not responding to an appropriate antibiotic treatment in 2 to 3 days should be reevaluated to ensure that the correct diagnosis the therapeutic drug concentrations are being achieved the patient is not immunosuppressed the patient does not have an isolated infection (i.e., abscess, foreign body) that resistance has not developed.

10. Systematic Approach for Selection of Antimicrobials 1. Confirm the presence of infection Careful history, physical Signs, symptoms and Predisposing factors 2. Identification of the pathogen Collection of infected material Stains Serologies Culture and sensitivity 10

11. Systematic Approach for Selection of Antimicrobials 11 3. Selection of presumptive therapy considering every infected site Host factors Drug factors 4. Monitor therapeutic response Clinical assessment Laboratory tests Assessment of therapeutic failure

12. 1.Confirming the Presence of Infection A. Fever is a controlled elevation of body temperature above the normal range is a hallmark of infectious diseases The average normal body temperature range taken orally is 36.7 to 37°C (98.0–98.6°F) rectally generally are 0.6°C (1°F) higher and axillary temperatures are 0.6°C (1°F) lower than oral temperatures Fever can be a manifestation of disease states other than infection 12

13. A. Fever Many drugs have been identified as causes of fever β - lactam antibiotics, anticonvulsants, allopurinol , hydralazine , nitrofurantoin , sulfonamides, phenothiazines , and methyldopa Drug-induced fever is defined as persistent fever in the absence of infection or other underlying condition Possible mechanisms of drug-induced fever hypersensitivity reaction development of antigen-antibody complexes that result in the stimulation of macrophages and the release of interleukin 1 (IL-1). 13

14. B. Signs and Symptoms white blood cell count Most infections result in elevated white blood cell (WBC) counts ( leukocytosis ) Elevated granulocyte counts (band neutrophils ) - Bacterial infections Lymphocytosis - tuberculosis and viral or fungal infections Increases in monocytes - tuberculosis or lymphoma Increases in eosinophils - allergic reactions, parasitic infection 14

15. White Blood Cell Count and Differential 15

16. B. Signs and Symptoms The most common granulocyte defect is neutropenia, a decrease in absolute numbers of circulating neutrophils (< 1000 cells/mm 3 ). Important risk factors for infe ction Degree or severity of neutropenia Rate of neutrophil decline Duration of neutropenia Erythrocyte sedimentation rate and C – reactive protein 16

17. B. Signs and Symptoms Local Signs The classic signs of pain and inflammation swelling, erythema , tenderness, and purulent drainage superficial or in a bone or joint infection Examining tissues or fluids inflammation in deep-seated infections Symptoms referable to an organ system must be sought out carefully, because they help in establishing the presence of infection aid in narrowing the list of potential pathogens 17

18. 2.Identification of the Pathogen A. Microbiology Issues Sample the infected materials produced by the patient e.g., blood, sputum, urine, stool, and wound or sinus drainage, spinal fluid and joint fluid Gram staining, serology, culture, sensitivity test B. Interpreting Results Be cautious in determining whether the organism recovered is a true pathogen, a contaminant, or a part of the normal flora 18

19. Classification of Infectious Organisms 19

20. Classification of Infectious Organisms 20

21. Site of Infection: Suspected Organisms 21

22. Site of Infection: Suspected Organisms 22

23. Site of Infection: Suspected Organisms 23

24. 3. Selection of Presumptive Therapy Factors to be considered during selection of antimicrobials : host factors factors related to the drugs used the severity and acuity of the disease the necessity for using multiple agents 24

25. 3. Selection of Presumptive Therapy A. Host Factors Age Pregnancy Drug allergies Genetic or metabolic abnormalities Renal and hepatic function Site of infection Concomitant drug therapy Underlying disease state Host defense 25

26. Major Drug Interactions with Antimicrobials 26

27. Major Drug Interactions with Antimicrobials 27

28. 3. Selection of Presumptive Therapy B. Drug Factors Tissue Penetration Drug Toxicity Cost Pharmacokinetic and Pharmacodynamic Considerations Combination of Antimicrobial Therapy 28

29. Combination of Antimicrobial Therapy Advantages of Combination Therapy Broadening the Spectrum of Coverage Synergism Preventing Resistance Decreased toxicity Disadvantages of Combination Therapy Increased cost Greater risk of drug toxicity Antagonistic effects 29

30. 4. Monitoring Therapeutic Response After antimicrobial therapy has been instituted The WBC count and temperature should start to normalize Physical complaints from the patient also should diminish i.e., decreased pain, shortness of breath, cough, or sputum production Appetite should improve Determine serum (or other fluid) levels of antimicrobials ensure outcome, prevent toxicity, or both Changes in the volume of distribution can have a significant impact on the efficacy, safety, or both of therapy 30

31. 4. Monitoring Therapeutic Response As patients improve clinically, the route of administration should be reevaluated. Criteria that should be present to justify a switch from IV to oral therapy include (1) overall clinical improvement (2) lack of fever for 8 to 24 hours (3) decreased WBC count (4) a functioning gastrointestinal tract 31

32. Failure of Antimicrobial Therapy Failures Caused by Drug Selection Failures Caused by Host Factors Failures Caused by Microorganisms Intrinsic resistance Acquired resistance (1) alteration in the target site (2) change in membrane permeability (3) efflux pump (4) drug inactivation 32

33. Antimicrobial Use Management Antibiotic Formulary Antimicrobial Cycling a predetermined change in an antimicrobial recommendation for empirical therapy of a specific infection at a predetermined time employed as a mechanism to reduce or prevent antimicrobial resistance Keeping Current 33

34. Upper respiratory infections 34

35. Objectives 35 Name the most common infectious pathogens in acute otitis media, sinusitis, and pharyngitis. Discuss the pathophysiology of acute otitis media, sinusitis, and pharyngitis. Develop a treatment plan for a patient with acute otitis media, sinusitis, and pharyngitis.

36. Outlines 36 Definitions Etiology Pathophysiology Clinical presentation Diagnosis Treatment Monitoring and evaluation

37. Acute Otitis Media Otitis media is an inflammation of the middle ear. There are three subtypes of otitis media: Acute otitis media (AOM) a symptomatic middle ear infection that occurs rapidly along with effusion, or presence of fluid. Otitis media with effusion (OME) fluid is present in the middle ear for an extended period in the absence of signs and symptoms of acute infection such as pain and a bulging eardrum. Chronic otitis media persistent or recurrent purulent otorrhoea (the discharge of pus from the ear) in the setting of tympanic membrane perforation 37

38. Epidemiology 38 Otitis media is most common in children between 6 months and 2 years of age but can occur in all age groups, including adults. 75% of infants and children will have at least one episode in the first 12 months of life.

39. Risk factors for AOM Viral respiratory tract infection Day-care attendance Siblings Allergy Male gender Tobacco smoke exposure Anatomic defects such as cleft palate Low socioeconomic status Lack of breastfeeding Young age at first diagnosis Immunodeficiency Positive family history 39

40. Etiology 40 Viral pathogens influenza virus, rhinovirus, and enterovirus (40% to 75%) Bacterial pathogens include: Streptococcus pneumoniae (25–50%) Haemophilus influenzae (15–30%) Moraxella catarrhalis (3–20%)

41. Antibiotic resistance 41 S. pneumoniae, H. influenzae, and M. catarrhalis can all possess resistance to β - lactams . The risk factors for amoxicillin-resistant bacteria in acute otitis media are: attendance at child care centers recent receipt of antibiotic treatment (within the past 30 days) age younger than 2 years.

42. Pathophysiology 42 Acute bacterial otitis media usually follows a viral upper respiratory tract infection that causes: Eustachian tube dysfunction mucosal swelling in the middle ear Bacteria that colonize the nasopharynx enter the middle ear and are not cleared properly by the mucociliary system The bacteria proliferate and cause infection

43. Pathophysiology 43 In otitis media, tympanic membrane becomes blocked with fluid, resulting in a bulging and erythematous tympanic membrane. Children tend to be more susceptible to otitis media than adults because, the anatomy of their Eustachian tube is shorter and more horizontal, facilitating bacterial entry into the middle ear

44. Clinical Presentation of acute otitis media 44 General Acute onset of signs and symptoms of middle ear infection following cold symptoms of runny nose, nasal congestion, or cough Signs and Symptoms Ear pain that can be severe (>75% of patients) Children may be irritable, tug on the involved ear, and have difficulty sleeping Fever is present in less than 25% of patients and, when present, occurs more often in younger children Examination shows a discolored (gray), thickened, bulging eardrum

45. Clinical Presentation of acute otitis media 45 Pneumatic otoscopy or tympanometry demonstrates an immobile eardrum; 50% of cases are bilateral Draining middle ear fluid occurs in less than 3% of patients and usually has a bacterial etiology Laboratory Tests Gram stain, culture, and sensitivities of draining fluid or aspirated fluid if tympanocentesis is performed

46. Diagnosis 46 Acute otitis media : acute onset of signs and symptoms, middle ear effusion, and middle ear inflammation. Middle ear effusion : bulging of the tympanic membrane, limited or absent mobility of the tympanic membrane, air-fluid level behind the tympanic membrane, or otorrhea.

47. Diagnosis 47 Middle ear inflammation: either distinct erythema of the tympanic membrane or distinct ear otalgia (or ear pain). A diagnosis is considered to be "uncertain" if the patient does not have all three of these diagnostic criteria. Severe AOM : Moderate to severe ear pain or fever of 39°C or greater. Nonsevere AOM : Mild ear pain and fever of less than 39°C in past 24 hours.

48. Complications of Otitis Media 48 Infectious : mastoiditis , meningitis, osteomyelitis , intracranial abscess Structural : perforated eardrum, cholesteatoma Hearing and/or speech impairment

49. Treatment 49 Desired Outcome Treatment goals include: pain management reducing signs and symptoms eradication of infection secondary disease prevention ( mastoiditis , bacteremia , meningitis, and auditory sequelae with the potential for speech and language impairment )

50. Treatment 50 General Approach to Treatment differentiate subtype of otitis media address pain with oral analgesics consider if a brief observation period is warranted or if the disease severity or patient characteristics require immediate antibiotic therapy If a bacterial infection is suspected, consider if the patient has risk factors for penicillin resistance.

51. Nonpharmacologic therapy 51 Analgesics / antipyretics Paracetamol , ibuprofen Eardrops with a local anesthetic, such as ametocaine , benzocaine, or lidocaine provide pain relief when administered with oral pain medication to children ages 3 to 18 years. Neither decongestants nor antihistamines should be routinely recommended in cases of acute otitis media or otitis media with effusion, Because of minimal benefit and increased side effects

52. Pharmacologic Therapy 52 Delayed Antimicrobial Therapy Antibiotic therapy for upper respiratory diseases must be balanced with possible increases in adverse drug events and increased antibiotic pressure. How ? - "delayed therapy.“ Delayed therapy a healthcare worker provides the patient with a prescription but encourages the patient to wait to use the medication for 48 to 72 hours to see if the symptoms will resolve on their own.

53. Delayed therapy 53 Candidates for delayed therapy include (a) children 6 months to 2 years of age without severe symptoms plus uncertain diagnosis (b) children 2 years and older without severe symptoms (c) children 2 years and older with an uncertain diagnosis.

54. 54 Treatment algorithm for initial antibiotics or observation in children with suspected or certain uncomplicated AOM

55. Acute Otitis Media Antibiotic Recommendations 55

56. Antibiotics 56 Amoxicillin- clavulanate ; 90 mg/kg/day of amoxicillin plus 6.4 mg/kg/day of clavulnate divided twice daily

57. Antibiotics 57 Duration of treatment Therapy for uncomplicated acute otitis media typically is administered for 5–7 days to patients ≥6 years old; longer courses (e.g., 10 days) should be reserved for children <6 years old and patients with severe disease, in whom short-course therapy may be inadequate.

58. Acute otitis media treatment (STG) 58 First line Amoxicillin, 500mg P.O. TID for 10 days for adults; 250 mg P.O. TID for 10 days for children above 6 years of age; 125mg/5ml, 250mg/5ml P.O. TID for 10 days for children under 6 years of age. Alternatives Ampicillin , Adults: 250–500mg P.O. QID for 10 days. Children: 50–100mg/kg P.O. QID OR 100-200mg/kg IV QID for 10 days OR Sulfamethoxazole+trimethoprim , Adults; 160+800mg. P.O. BID for 10 days. Children 6 12 years of age; 80+400mg P.O. BID for 10 days OR

59. Acute otitis media treatment (STG) 59 Amoxicillin/ Clavulanate , 375mg P.O. TID for 10 days OR 625mg P.O. BID for 10 days for adults 312mg/5ml suspension P.O. TID for 10 days OR 156mg/5ml suspension P.O. TID for 10 days for children OR Erythromycin, Adults; 250mg to 500mg P.O. QID. Children; 30-50mg/kg P.O. QID OR 15-20mg/kg IV Q 4 to 6hours. For pain: Paracetamol , 30-40mg/kg in 4-6 divided doses in 24hrs.

60. Recurrent acute otitis media 60 Recurrent acute otitis media is defined as at least three episodes in 6 months or at least four episodes in 12 months. Recurrent infections are of concern because patients younger than 3 years are at high risk for hearing loss and language and learning disabilities. Surgical insertion of tympanostomy tubes (T-tubes) Delay treatment until the onset of symptoms Limit antibiotic prophylaxis to 6 months' duration

61. Evaluation of Therapeutic Outcomes 61 Patients with acute otitis media should be reassessed after 3 days Pain and fever tend to resolve after 2 or 3 days, with most children becoming asymptomatic at 7 days Treatment failure is a lack of clinical improvement in the signs and symptoms of infection, including pain, fever, and erythema /bulging of the tympanic membrane, after 3 days If antibiotics were withheld initially, they should be instituted now. If the patient initially received an antibiotic, then the antibiotic should be changed

62. Evaluation of Therapeutic Outcomes 62 Early reevaluation of the eardrum when signs and symptoms are improving can be misleading because effusions persist. Over a period of 1 week, changes in the eardrum normalize, and the pus becomes serous fluid. Air-fluid levels are apparent behind the eardrum, at which point the stage is now referred to as otitis media with effusion. This does not represent ongoing infection, nor are additional antibiotics required. Immediate reevaluation is appropriate if hearing loss results from persistent middle ear effusions following infection.

63. Case 63 A 15-month-old girl presents to the pediatric clinic with 2 days of fever (38.9°C), runny nose, and fussiness. Her mother states that she is more irritable than usual and cries many times throughout the night. She is not as interested in eating today. She attends day care and has a 5-year-old brother who recently had a cold. Physical examination reveals erythema and bulging of the right tympanic membrane and the presence of middle ear fluid. What information is suggestive of AOM? Does the child have risk factors for AOM?

64. Acute Bacterial Sinusitis 64 Sinusitis is an inflammation and/or infection of the paranasal sinuses, or membrane-lined air spaces, around the nose. Rhinosinusitis involves inflammation of sinus and contiguous nasal mucosa.

65. Paranasal sinuses 65 Four pairs of paranasal sinuses Frontal-above eyes in forehead bone Maxillary-in cheekbones, under eyes Ethmoid -between eyes and nose Sphenoid-in center of skull, behind nose and eyes

66. 66 Paranasal Sinuses

67. Epidemiology 67 Children have six to eight viral upper respiratory tract infections per year, yet only 5% to 13% of these are complicated by a secondary bacterial sinusitis infection. Only 0.5% to 2% of viral upper respiratory tract infections in adults are complicated by sinusitis.

68. Etiology 68 Viruses are responsible for most cases of acute sinusitis(rhinovirus, influenza virus, and respiratory syncytial virus). When symptoms persist for 7 days or more or become severe, bacteria may be a primary or secondary cause of infection S. pneumoniae and H. influenzae – 70% M. catarrhalis – 25% Streptococcus pyogenes , Staphylococcus aureus , fungi, and anaerobes are associated less frequently

69. Classification of bacterial sinusitis 69 Bacterial sinusitis can be categorized into acute and chronic disease. Acute sinusitis lasts less than 30 days with complete resolution of symptoms. Acute bacterial rhinosinusitis (ABRS) refers to an acute bacterial infection of the sinuses that can occur independently or be superimposed on chronic sinusitis. Chronic sinusitis is defined as episodes of inflammation lasting more than 3 months with persistence of respiratory symptoms ( cough, rhinorrhea ).

70. Pathophysiology 70 Acute bacterial sinusitis usually is preceded by a viral respiratory tract infection that causes mucosal inflammation. This can lead to obstruction of the sinus ostia —the pathways that drain the sinuses. This environment is ideal for bacterial growth and promotes a cycle of local inflammatory response and mucosal injury characterized by increased concentrations of interleukins, histamine, and tumor necrosis factor.

71. Pathophysiology 71 Mucosal secretions become trapped, local defenses are impaired, and bacteria from adjacent surfaces begin to proliferate. The maxillary and ethmoid sinuses are the ones most frequently involved. In some patients, chronic symptoms develop after acute infection; Either by more persistent pathogens or a subtle defect in the host's immune function.

72. Clinical Presentation 72 General A nonspecific upper respiratory tract infection that persists beyond 7 to 14 days Signs and Symptoms Acute: Adults Nasal discharge/congestion Maxillary tooth pain, facial or sinus pain that may radiate (unilateral in particular), as well as deterioration after initial improvement Severe or persistent (>7 days) signs and symptoms are most likely bacterial and should be treated with antibiotics

73. Clinical Presentation 73 Children Nasal discharge and cough for longer than 10 to 14 days or severe signs and symptoms such as temperature above 39°C (102°F) or facial swelling or pain are indications for antibiotic therapy

74. Clinical Presentation 74 Chronic Symptoms are similar to acute sinusitis but more nonspecific Rhinorrhea is associated with acute exacerbations Chronic unproductive cough, laryngitis, and headache may occur Chronic/recurrent infections occur three or four times per year and are unresponsive to steam and decongestants Laboratory Tests Gram stain, culture, and sensitivities of draining fluid or aspirated fluid if sinus puncture is performed

75. Treatment 75 Desired outcome Treatment goal the reduction in signs and symptoms achieving and maintaining patency of the ostia limiting antimicrobial treatment to those who may benefit eradication of bacterial infection with appropriate antimicrobial therapy minimizing the duration of illness prevention of complications prevention of progression from acute disease to chronic disease.

76. Treatment 76 General Approach to Treatment delineate viral and bacterial sinusitis based on disease duration Bacterial sinusitis may also be suspected if symptoms do not respond to nonprescription nasal decongestants and acetaminophen.

77. Treatment – general approach 77 Decide whether the infection is complicated or uncomplicated complicated if the patient has mental status changes, immunosuppressive illness, unilateral findings, significant coexisting illnesses, risk factors for β - lactam -resistant strains, history of antibiotic failure, isolated frontal or sphenoid sinusitis, or intense periorbital swelling, erythema , and facial pain …. (Refer to specialist)

78. Abbreviated Definitions for Evidence-Based Statements 78

79. Abbreviated Guideline Statements for Acute Bacterial Sinusitis 79

80. Nonpharmacologic Therapy 80 Many symptoms of sinusitis will resolve within 48 hours without medical therapy. Nasal decongestant sprays phenylephrine and oxymetazoline Use should be limited to no more than 3 days to prevent the development of tolerance and/or rebound congestion Irrigation of the nasal cavity with saline and steam inhalation may be used to increase mucosal moisture Mucolytics (e.g., guaifenesin ) may be used to decrease the viscosity of nasal secretions

81. Nonpharmacologic Therapy 81 Antihistamines should not be used for acute bacterial sinusitis due to of their anticholinergic effects that can dry mucosa and disturb clearance of mucosal secretions. Second-generation antihistamines may play a role in chronic sinusitis, which is frequently accompanied by concomitant allergic rhinitis. Glucocorticoids intranasally may decrease inflammation causing headache, nasal congestion, and facial pain; however, there are limited data to support their use in acute sinusitis.

82. Pharmacologic Therapy 82

83. Oral Dosing Guidelines for Acute Bacterial Sinusitis 83

84. Antibiotics 84 Duration of treatment The current recommendations are 10 to 14 days of antibiotic therapy or at least 7 days after signs and symptoms are under control.

85. Antibiotics (STG) 85 First line Amoxicillin , Adults; 250 - 500mg (depending on the severity) P.O. TID for 10 days. Alternative Amoxicillin + Clavulanate , Adults; 375mg P.O. TID for 10 days OR 625mg P.O. BID for 10 days (depending on the severity). Children; 156mg /5ml or 312mg/5ml P.O. TID OR Sulfamethoxazole + trimethoprim 800mg/160 mg. P.O.BID for 7 days. For children 6 weeks – 5 months, 100/20 mg; 6 months – 5 yrs, 200/40 mg; 6 – 12 yrs, 400/80 mg BID. OR Erythromycin, Adults; 250-500mg P.O. QID. Children 30-50mg/kg P.O. QID

86. Evaluation of Therapeutic Outcomes 86 Persistent or worsening symptoms 72 hours after initiating antibiotic therapy should be considered treatment failure. Patients who experience changes in visual acuity or mental status should be referred immediately. Surgery may be considered in more complicated patients.

87. Acute Pharyngitis 87 Pharyngitis is an acute infection of the oropharynx or nasopharynx . Epidemiology Acute pharyngitis accounts for 2 million emergency department and outpatient department visits per year, at a cost of approximately $1.2 billion total and up to $539 million for children alone. Children ages 5 to 15 years are most susceptible. Parents of school-age children and those who work with children are at increased risk.

88. Etiology 88 Viruses rhinovirus (20%), coronavirus (<5%), adenovirus (5%), herpes simplex virus (4%), influenza virus (2%), parainfluenza virus (2%), and Epstein-Barr virus (<1%)

89. Etiology 89 Bacterial causes GABHS (group A β -hemolytic streptococci, also known as S. pyogenes ), is the most common (10–30% of persons of all ages) Pediatric population, GABHS causes 15% to 30% Adults, GABHS is responsible for 5% to 15% less-common causes of acute pharyngitis are: groups C and G Streptococcus, Corynebacterium diphtheriae , Neisseria gonorrhoeae , Mycoplasma pneumoniae, Arcanobacterium haemolyticum , Yersinia enterocolitica , and Chlamydia pneumoniae

90. Pathophysiology 90 Asymptomatic pharyngeal carriers of the organism may have an alteration in host immunity (e.g., a breach in the pharyngeal mucosa) and the bacteria of the oropharynx , allowing colonization to become an infection. Pathogenic factors associated with the organism itself may also play a role. These include pyrogenic toxins, hemolysins , streptokinase, and proteinase .

91. Clinical Presentation 91 General A sore throat of sudden onset that is mostly self-limited Fever and constitutional symptoms resolving in about 3 to 5 days Clinical signs and symptoms are similar for viral causes and non streptococcal bacterial causes

92. Clinical presentation 92 Signs and Symptoms Sore throat Pain on swallowing Fever Headache, nausea, vomiting, and abdominal pain (especially children) Erythema /inflammation of the tonsils and pharynx with or without patchy exudates Enlarged, tender lymph nodes Red swollen uvula, petechiae on the soft palate, and a scarlatiniform rash Several symptoms that are not suggestive of group A streptococci are cough, conjunctivitis, coryza , and diarrhea

93. Clinical presentation 93 Signs Suggestive of Viral Origin for Pharyngitis Conjunctivitis Coryza Cough Diarrhea Laboratory Tests Throat swab and culture Rapid antigen detection testing (RADT)

94. Treatment 94 Desired Outcome Treatment goal to improve clinical signs and symptoms to minimize adverse drug reactions to prevent transmission to close contacts to prevent acute rheumatic fever and suppurative complications, such as peritonsillar abscess, cervical lymphadenitis, and mastoiditis .

95. Nonpharmacologic Therapy 95 Supportive care antipyretic medications (e.g. paracetamol ) nonprescription lozenges and sprays containing menthol and topical anesthetics for temporary relief of pain

96. Pharmacologic Therapy 96 Because penicillin has a narrow spectrum of activity and is readily available, safe, and inexpensive, it is considered the treatment of choice. The only controlled studies that have demonstrated that antibiotic therapy prevents rheumatic fever following GABHS pharyngitis were done with procaine penicillin, which was later replaced with benzathine penicillin.

97. Dosing Guidelines for Pharyngitis 97

98. Antibiotics and Dosing for Recurrent Episodes of Pharyngitis 98

99. Evaluation of Therapeutic Outcomes 99 fever and other symptoms resolve within 3 or 4 days of onset without antibiotics symptoms will improve 16 hours to 21/2 days earlier with antibiotic therapy for patients who remain symptomatic or when symptoms recur despite completion of treatment, posttreatment throat cultures 2 to 7 days after completion of antibiotics should be done

100. 100 Lower respiratory infections

101. Objectives 101 Identify host defenses for preventing lower respiratory tract infections. Discuss the epidemiology, etiology, and pathogenesis of common lower respiratory tract infections. Compare and contrast the clinical manifestations of various lower respiratory tract infections. Recommend appropriate nonpharmacological and pharmacological therapy for the treatment of lower respiratory tract infections. Apply knowledge of prescribed antimicrobials in providing patient-specific counseling in order to optimize therapy .

102. Outlines 102 Definitions Etiology Pathophysiology Clinical presentation Diagnosis Treatment Monitoring and evaluation

103. Introduction 103 The respiratory tract has an elaborate system of host defenses, including: humoral immunity cellular immunity anatomic mechanisms When functioning properly the host defenses of the respiratory tract are markedly effective in: protecting against pathogen invasion removing potentially infectious agents from the lungs

104. Introduction 104 Infections in the lower respiratory tract occur: when the defense mechanisms are impaired when a particularly virulent microorganism invades lung parenchyma The majority of pulmonary infections follow colonization of the upper respiratory tract with potential pathogens, which gain access to the lung via aspiration of oropharyngeal secretions. Less commonly, microbes enter the lung via the blood from an extrapulmonary source or by inhalation of infected aerosolized particles.

105. Bronchitis 105 Bronchitis is inflammatory conditions of the large elements of the tracheobronchial tree. The inflammatory process does not extend to the alveoli. Bronchitis frequently is classified as acute or chronic.

106. Acute Bronchitis 106 Etiology Respiratory viruses are by far the most common infectious agents rhinovirus and coronavirus influenza virus and adenovirus Bacterial causes M. pneumoniae C. pneumoniae (also referred to as Chlamydophila ) B. pertussis

107. Pathogenesis 107 Infection of the trachea and bronchi yields hyperemic and edematous mucous membranes with an increase in bronchial secretions. Destruction of respiratory epithelium can range from mild to extensive and may affect bronchial mucociliary function. In addition, the increase in desquamated epithelial cells and bronchial secretions, which can become thick and tenacious, further impairs mucociliary activity.

108. Pathogenesis 108 Recurrent acute respiratory infections may be associated with increased airway hyperreactivity and possibly the pathogenesis of asthma or chronic obstructive pulmonary disease (COPD).

109. Clinical Presentation 109 Acute bronchitis usually begins as an upper respiratory infection. The patient typically has nonspecific complaints such as malaise and headache, coryza , and sore throat. Cough is the hallmark of acute bronchitis and occurs early onset of cough may be insidious or abrupt persist for up to 3 or more weeks despite resolution of nasal or nasopharyngeal complaints the cough initially is nonproductive but then progresses, yielding mucopurulent sputum

110. Clinical presentation 110 Dyspnea , cyanosis, or signs of airway obstruction are observed rarely

111. Treatment 111 The goals of therapy are: to provide comfort to the patient to treat associated dehydration and respiratory compromise, in the unusually severe case

112. General Approach to Treatment 112 Treatment of acute bronchitis is symptomatic and supportive in nature. Reassurance and antipyretics Bed rest for comfort drinking fluid to prevent dehydration Mist therapy (use of a vaporizer) may promote the thinning and loosening of respiratory secretions.

113. Pharmacologic Therapy 113 Mild analgesic–antipyretic therapy to relieve associated lethargy, malaise, and fever Aspirin or acetaminophen (650 mg in adults or 10 to 15 mg/kg per dose in children; maximum daily pediatric dose 60 mg/kg; maximum daily adult dose 4 g) or Ibuprofen (200 to 800 mg in adults or 10 mg/kg per dose in children; maximum daily pediatric dose 40 mg/kg; maximum daily adult dose 3.2 g) administered every 4 to 6 hours.

114. Pharmacologic Therapy 114 Persistent, mild cough, which may be bothersome, can be treated with dextromethorphan Dextromethorphan hydrobromide ,15 – 30 mg P.O. TID to QID for adults. For children: 6-12 yrs, 7.5-15 mg; 2-6 yrs, 7.5 mg TID or QID More severe coughs may require intermittent codeine or other similar agents Codeine phosphate , 10 - 20 mg P.O TID or QID. For children: 0.5 mg/kg P.O. QID

115. Pharmacologic Therapy 115 Routine use of antibiotics for treatment of acute bronchitis should be discouraged In previously healthy patients who exhibit persistent fever or respiratory symptoms for more than 4 to 6 days or for predisposed patients (e.g., elderly, immunocompromised ) the possibility of a concurrent bacterial infection should be suspected. Azithromycin levofloxacin

116. Antibiotics for acute bronchitis 116 First line: Amoxicillin, 250- 500 mg P.O.TID for adults. For children: 20 – 40 mg/kg/day P.O. in 3 divided doses. Alternative Ampicillin , 500 mg P.O. QD, in 4-divided dose for 5-7 Sulfamethoxazole+trimethoprim , 800mg/160 mg. P.O.BID for 7 days. For children 6 weeks – 5 months, 100/20 mg; 6 months – 5 yrs, 200/40 mg; 6 – 12 yrs, 400/80 mg BID. Erythomycin , 250-500 mg P.O. QID for 7 days. For children: 30-50 mg/kg/day P.O. in 4 divided doses; 15-20 mg/kg/day IV over 5 minutes in 3-4 divided doses.

117. Chronic Bronchitis 117 Chronic bronchitis is defined clinically as the presence of a chronic cough productive of sputum lasting more than 3 consecutive months of the year for 2 consecutive years without an underlying etiology of bronchiectasis or tuberculosis. The contributing factors for the disease include: cigarette smoking, exposure to occupational dusts, fumes, and environmental pollution and host factors [e.g., genetic factors and bacterial (and possibly viral) infections].

118. Pathogenesis 118 Chronic inhalation of an irritating noxious substance compromises the normal secretory and mucociliary function of bronchial mucosa. The bronchial wall is thickened, and the number of mucus-secreting goblet cells on the surface epithelium of both larger and smaller bronchi is increased markedly. Hypertrophy of the mucous glands and dilation of the mucous gland ducts are observed. more mucus in their peripheral airways mucous plugging of the smaller airways

119. Pathogenesis 119 Continued progression of this pathology can result in: residual scarring of small bronchi augmenting airway obstruction the weakening of bronchial walls

120. Clinical Presentation 120 Cough (the hallmark) Cyanosis Expectoration of the largest quantity of sputum usually occurs upon arising in the morning. Tenacious color from white to yellow-green Patients with chronic bronchitis often expectorate as much as 100 mL /day more than normal. As a result, develop bad taste in their mouth and of halitosis

121. Clinical Presentation 121 Physical examination Chest auscultation usually reveals inspiratory and expiratory rales , rhonchi , and mild wheezing with an expiratory phase that is frequently prolonged. There is hyperresonance on percussion with obliteration of the area of cardiac dullness. Normal vesicular breathing sounds are diminished. Clubbing of digits (advanced disease). Chest radiograph Increase in the anteroposterior diameter of the thoracic cage (observed as a barrel chest) Depressed diaphragm with limited mobility

122. Clinical Presentation 122 Laboratory tests Erythrocytosis (advanced disease) Pulmonary function tests Decreased vital capacity Prolonged expiratory flow

123. Common Bacterial Pathogens Isolated from Sputum of Patients with Acute Exacerbation of Chronic Bronchitis 123 Ser No Pathogen Percent of cultures 1 H. influenzae   45 2 M. catarrhalis   30 3 S. pneumoniae 20 4 E.coli, Enterobacter species, Klebsiella species, P. aeruginosa   5

124. Treatment 124 Desired outcome The goals of therapy for chronic bronchitis are twofold: to reduce the severity of chronic symptoms to ameliorate acute exacerbations and achieve prolonged infection-free intervals.

125. Pharmacologic Therapy 125 A therapeutic challenge of β 2 -agonist bronchodilators perform Pulmonary function tests before and after β 2 -agonist aerosol administration Regular use of a long-acting β -receptor agonist aerosol (e.g., salmeterol , formoterol ) in responsive patients may be more effective and probably more convenient than short-acting β 2 -receptor agonists. Long-term inhalation of ipratropium has been associated with a decreased frequency of cough, less severe coughing, and a decrease in the volume of expectorated sputum.

126. Pharmacologic Therapy 126 Use of antimicrobials for treatment of chronic bronchitis has been controversial but is becoming more accepted. Anthonisen criteria to determine if antibiotic therapy is indicated. If a patient exhibits two of the following three criteria during an acute exacerbation of chronic bronchitis, antibiotic therapy is recommended. (1) increase in shortness of breath (2) increase in sputum volume (3) production of purulent sputum.

127. Oral Antibiotics Commonly Used for the Treatment of Acute Respiratory Exacerbations in Chronic Bronchitis 127

128. Pharmacologic Therapy 128 Duration of treatment 5-7 days

129. Bronchiolitis 129 Bronchiolitis is an acute viral infection of the lower respiratory tract that affects approximately 50% of children during the first year of life and 100% by age 3 years. Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis , accounting for up to 75% of all cases. Other detectable viruses include parainfluenza , adenovirus, and influenza. Bacteria serve as secondary pathogens in a minority of cases.

130. Clinical Presentation 130

131. Treatment 131 Bronchiolitis is a self-limiting illness. usually requires no therapy (other than reassurance and antipyretics) unless the infant is hypoxic or dehydrated. Healthy infants can be treated for fever, provided generous amounts of oral fluids, and observed closely. In severely affected children, the mainstays of therapy for bronchiolitis are oxygen therapy and IV fluids.

132. Pharmacological therapy 132 Aerosolized β 2 -adrenergic therapy appears to offer little benefit for the majority of patients and may even be detrimental. Ribavirin may be considered for bronchiolitis caused by respiratory syncytial virus in a subset of patients (those with underlying pulmonary or cardiac disease or with severe acute infection).

133. Pneumonia 133 Pneumonia is an infectious inflammation of the lung parenchyma.

134. Pneumonia 134 Pathophysiology Microorganisms gain access to the lower respiratory tract by three routes: inhaled as aerosolized particles they may enter the lung via the bloodstream from an extrapulmonary site of infection aspiration of oropharyngeal contents may occur. Mechanical factors are critically important in host defense. The hairs and turbinates of the nares capture larger inhaled particles before they reach the lower respiratory tract.

135. Pathophysiology 135 The branching architecture of the tracheobronchial tree traps particles on the airway lining, where mucociliary clearance and local antibacterial factors either clear or kill the potential pathogen. The gag reflex and the cough mechanism offer critical protection from aspiration. In addition, the normal flora adhering to mucosal cells of the oropharynx , whose components are remarkably constant, prevents pathogenic bacteria from binding and thereby decreases the risk of pneumonia caused by these more virulent bacteria.

136. Pathophysiology 136 When these barriers are overcome or when the microorganisms are small enough to be inhaled to the alveolar level, resident alveolar macrophages are extremely efficient at clearing and killing pathogens. Macrophages are assisted by local proteins (e.g., surfactant proteins A and D) that have intrinsic opsonizing properties or antibacterial or antiviral activity. Once engulfed by the macrophage, the pathogens—even if they are not killed—are eliminated via either the mucociliary elevator or the lymphatics and no longer represent an infectious challenge.

137. Pathophysiology 137 Lung infections with viruses suppress the antibacterial activity of the lung by impairing alveolar macrophage function and mucociliary clearance, thus setting the stage for secondary bacterial pneumonia. Mucociliary transport is also depressed by ethanol and narcotics and by obstruction of a bronchus by mucus, tumor, or extrinsic compression.

138. Pathophysiology 138 Only when the capacity of the alveolar macrophages to ingest or kill the microorganisms is exceeded does clinical pneumonia become manifest. In that situation, the alveolar macrophages initiate the inflammatory response to bolster lower respiratory tract defenses. The host inflammatory response, rather than the proliferation of microorganisms, triggers the clinical syndrome of pneumonia.

139. Pathophysiology 139 The release of inflammatory mediators, such as interleukin (IL)-1 and tumor necrosis factor (TNF), results in fever. Chemokines , such as IL-8 and granulocyte colony-stimulating factor, stimulate the release of neutrophils and their attraction to the lung, producing both peripheral leukocytosis and increased purulent secretions.

140. Classification of pneumonia 140 Community-acquired pneumonia (CAP) Cases of infectious pneumonia in patients living independently in the community Patients who have been hospitalized for other reasons for less than 48 hours before the development of respiratory symptoms The most prominent pathogen causing community-acquired pneumonia in otherwise healthy adults is S. pneumoniae and accounts for up to 75% of all acute cases. It is particularly prevalent and severe for patients with splenic dysfunction, diabetes mellitus, chronic cardiopulmonary or renal disease, or HIV infection.

141. Community-acquired pneumonia (CAP) 141 Community-acquired disease with S. aureus is identified most frequently in young infants, patients with early cystic fibrosis, and those recovering from an antecedent respiratory viral infection. Other common pathogens include M. pneumoniae, Legionella species, C. pneumoniae, H. influenzae, and a variety of viruses including influenza.

142. Community-acquired pneumonia (CAP) 142 Risk factors Age >65 years Diabetes Mellitus Asplenia Chronic cardiovascular, pulmonary, renal and/or liver disease Smoking and/or alcohol abuse

143. Healthcare-associated pneumonia (HCAP) 143 Pneumonia developing in patients not in medical facility but two or more risk factors for MDR pathogens[e.g., P. aeruginosa , Acinetobacter species, and methicillin -resistant S. aureus (MRSA)] Risk factors Recent hospitalization 2 days within past 90 days Nursing home or long-term care facility resident Recent (past 30 days) antibiotic use, chemotherapy, wound care or infusion therapy either at a healthcare facility or home Hemodialysis patients Contact with a family member with infection caused by MDR pathogen

144. Hospital-acquired pneumonia (HAP) 144 Patients who have been hospitalized for at least 2 days Gram-negative aerobic bacilli, S. aureus , enteric (e.g., K . pneumoniae or E. coli ) and nonenteric (e.g., P. aeruginosa ) pathogens are the leading causative agents in hospital-acquired pneumonia (HAP). Patients with longer lengths of hospital admission prior to the development of HAP are more likely to have MDR organisms. The diagnosis of HAP usually is established by the presence of a new infiltrate on chest radiograph, fever, worsening respiratory status, and the appearance of thick, neutrophil -laden respiratory secretions.

145. Hospital-acquired pneumonia (HAP) 145 Risk factors Witnessed aspiration COPD, or coma Supine position Enteral nutrition, nasogastric tube Reintubation , tracheostomy , or patient transport Prior antibiotic exposure Head trauma, ICP monitoring Age >60 years The strongest predisposing factor is mechanical ventilation (intubation).

146. Ventilator-associated pneumonia (VAP) 146 Patients contracting pneumonia greater than 48 hours after the institution of endotracheal intubation and mechanical ventilation Ventilator-associated pneumonia (VAP) is also associated with MDR pathogens. Risk factors Same as HAP Anaerobic bacteria ( Peptostreptococcus species, Fusobacteria , B. melaninogenicus , B. fragilis ) are the most common etiologic agents in pneumonia that follows the gross aspiration of gastric or oropharyngeal contents.

147. Micro organisms causing pneumonia in infants and children 147 Pneumonia in infants and children is mostly caused by a nonbacterial pathogens. Most pneumonias occurring in the pediatric age group are caused by viruses, especially Respiratory syncytial virus ( RSV), parainfluenza , and adenovirus. M. pneumoniae is an important pathogen in older children. Beyond the neonatal period, S. pneumoniae is the major bacterial pathogen in childhood pneumonia, followed by group A Streptococcus and S. aureus . H. influenzae type b.

148. Clinical presentation 148 Signs and symptoms  Abrupt onset of fever, chills, dyspnea , and productive cough Rust-colored sputum or hemoptysis Pleuritic chest pain Physical examination  Tachypnea and tachycardia Dullness to percussion Chest wall retractions and grunting respirations Diminished breath sounds over affected area Inspiratory crackles during lung expansion

149. Clinical presentation 149 Chest radiograph  Dense lobar or segmental infiltrate Laboratory tests  Leukocytosis with predominance of polymorphonuclear cells Low oxygen saturation on arterial blood gas or pulse oximetry

150. Treatment 150 Desired Outcome Eradication of the offending organism through selection of the appropriate antibiotic complete clinical cure

151. General Approach to Treatment 151 The first priority in assessing the patient with pneumonia is to evaluate the adequacy of respiratory function and to determine the presence of signs of systemic illness, specifically dehydration or sepsis with resulting circulatory collapse. Oxygen or, in severe cases, mechanical ventilation and fluid resuscitation should be provided as necessary.

152. General Approach to Treatment 152 Administration of bronchodilators ( albuterol ) when bronchospasm is present, and chest physiotherapy with postural drainage if evidence of retained secretions is present. Adequate hydration (intravenously if necessary), optimal nutritional support, and control of fever. Appropriate sputum samples may be obtained to determine the microbiologic etiology Selection of an appropriate antimicrobial

153. 153

154. Evidence-Based Empiric Antimicrobial Therapy for Pneumonia in Adults 154

155. Evidence-Based Empiric Antimicrobial Therapy for Pneumonia in Adults 155

156. Evidence-Based Empiric Antimicrobial Therapy for Pneumonia in Adults 156

157. Home work 157 Refer STG for General Hospital of FDRE and write the dosage, frequency of administration, route of administration and duration of treatment of drugs used to treat different types of pneumonia.

158. Empirical Antimicrobial Therapy for Pneumonia in Pediatric Patients 158

159. Antibiotic Doses for Treatment of Bacterial Pneumonia 159

160. Antibiotic Doses for Treatment of Bacterial Pneumonia 160

161. Classification of the severity of pneumonia in pediatrics 161

162. Classification of the severity of pneumonia in pediatrics 162

163. Treatment 163 Very severe pneumonia Give ampicillin (50 mg/kg IV/IM every 6 hours) and gentamicin (7.5 mg/kg IM once a day) for 5 days; then, if child responds well, complete treatment at home or in hospital with oral amoxicillin (15 mg/kg three times a day) plus IM gentamicin once daily for a further 5 days. Alternatively, give chloramphenicol (25 mg/kg IM or IV every 6 hours) until the child has improved. Then continue orally 4 times a day for a total course of 10 days. Or use ceftriaxone (80 mg/kg IM or IV once daily) for the same duration

164. Treatment 164 If the child does not improve within 48 hours, switch to gentamicin (7.5 mg/kg IM once a day) and cloxacillin (50 mg/kg IM or IV every 6 hours), for staphylococcal pneumonia. When the child improves, continue gentamycin IM daily for a total of 10 days and cloxacillin (or dicloxacillin ) orally 4 times a day for a total course of 3 weeks.

165. Treatment 165 Complications or other diagnoses to be considered Treat with cloxacillin (50 mg/kg IM or IV every 6 hours) and gentamicin (7.5 mg/kg IM or IV once a day). When the child improves, continue gentamycin IM daily for a total of 10 days and cloxacillin orally 4 times a day for a total course of 3 weeks.

166. Treatment 166 Severe pneumonia Give benzyl penicillin (50 000 units/kg IV every 4 hours) for at least 3 days. (Don’t skip a dose if getting an IV route is difficult but give that dose IM) When the child improves, switch to oral amoxicillin (25 mg/kg 2 times a day). The total course of treatment is 5-7 days. If the child does not improve within 48 hours, or deteriorates, look for complications and treat accordingly. If there are no apparent complications, switch to chloramphenicol (25 mg/kg every 6 hours IM or IV) until the child has improved. Then continue orally for a total course of 10 days.

167. Treatment 167 Pneumonia ( non – severe) Give cotrimoxazole (4 mg/kg trimethoprim / 20 mg/kg sulfamethoxazole twice a day) for 5-7 days. In children who are receiving PCP prophylaxis, treat with Amoxicillin. Give the first dose at the clinic and teach the mother how to give the other doses at home.

168. Evaluation of Therapeutic Outcomes 168 For patients with CAP or pneumonia from any source of mild to moderate clinical severity, the time to resolution of cough, decreasing sputum production, and fever, as well as other constitutional symptoms of malaise, nausea, vomiting, and lethargy, should be noted. Initial resolution should be observed within the first 2 days and progression to complete resolution within 5 to 7 days but usually no more than 10 days. If the patient requires supplemental oxygen therapy, the amount and need should be assessed regularly.

169. Evaluation of Therapeutic Outcomes 169 For patients with HAP/HCAP Resolution of symptoms should be observed within 2 days of instituting antibiotic therapy. If no resolution of symptoms is observed within 2 days of starting seemingly appropriate antibiotic therapy or if the patient's clinical status is deteriorating, the appropriateness of initial antibiotic therapy should be critically reassessed

170. 170 QUESTION 1: M.R. is a 33-year-old man presenting to the ED yvith fevers, chills, and chest pain. His symptoms have persisted for 3 days, and he has a productive cough with rusty-colored sputum and dyspnea with exertion. He has had' no recent illnesses and no known sick contacts, but he was recently released from a 2-year period of incarceration. He has tried ibuprofen to alleviate his fever and chest pain. Past medical history is positive for asthma, for which he is prescribed fluticasone and albuterol , and depression, for which he takes sertraline . Vital signs reveal a temperature of 40.1 °C, heart rate of 128 beats/minute, blood pressure of 130176 mm Hg, and respiratory rate of 32 breaths/minute with accompanying oxygen saturations of 85% on 5 Lof oxygen by nasal cannula .

171. 171 The remainder of the physical examination is notable for orientation to person but not place or time and for diffuse crackles bilaterally, which are most apparent on the right side. Laboratory results include the following: WBC count, 15,500 cells/ ut , Hematocrit , 29.3% Sodium, 133 mmol /L Potassium, 3.8 mmol /L BUN, 23 mg/ dL SCr , 0.8 mg/ dL Glucose 148, mg/ dL pH 7.42 P02, 61 mm Hg Peo2, 46 mm Hg HC03, 28 mEq /L A test for human immunodeficiency virus is negative. Chest radiograph reveals a right lower lobe infiltrate. What signs, symptoms, and tests are consistent with CAP in M.R .? What pathogens are most likely in M.R.? Which antimicrobial agent(s) should be chosen for the initial management of M.R.?

172. References 172 Dipiro JT, Talbert RL, Yee GC, et.al. Pharmacotherapy, A Pathophysiologic Approach, 8th edition, Koda - Kimble MA, Young LY, Kradjan WA, et.al. Applied Therapeutics, The Clinical Use of Drugs, 9 th edition, 2009. DACA, STG for General Hospitals, 2010 FDRE, WHO. Pediatric Hospital Care: ETHIOPIA. Guidelines for the Management of Common Illnesses in Hospitals, First Edition, 2010.