Pharmacotherapy of Infectious Diseases PHMD 352 PDF

PHMD 352 PHARMACOTHERAPY OF INFECTIOUS  DISEASES Thelma Ohene-Agyei, PhD Department of Pharmacy Practice & Clinical Pharmacy  Course Outline    TOPICS ▪ Antimicrobial selection ▪ Skin Infecions ▪ STI...

PHMD 352 PHARMACOTHERAPY OF INFECTIOUS  DISEASES Thelma Ohene-Agyei, PhD Department of Pharmacy Practice & Clinical Pharmacy  Course Outline    TOPICS ▪ Antimicrobial selection ▪ Skin Infecions ▪ STIs  Discussion Points for Diseases  What it is Interventions: Pharmacologic & Non- Pharmacologic Aetiology & Epidemiology Drug therapy issues: Adherence, Drug Symptoms Interactions, Adverse effects Diagnostic tests Monitoring effectiveness & safety Goals/ Desired Therapeutic The role of the pharmacist   Assessment Assignments 10% Interim Assessments 30% Examination 60%  GROUP PRESENTATIONS 15 groups of 4-5 people each 15 minutes for each group to present The presentation should cover discussion points   TOPICS Conjuctivitis 1. Yaws 2. Acne Tonsilitis 3. Measles Gonorrhoea 4. Monkey pox Syphillis 5. Cellulitis 6. Otitis media Chlamydia 7. Rhinitis Herpes simplex 8. Sinusitis Hepatitis Antimicrobial Regimen  Selection Thelma Ohene-Agyei, PhD   Introduction Correct selection, use, and monitoring of clinical response of antibiotics is important- WHY? Guiding principles: ▪ Make the correct diagnosis ▪ Do no harm!   Goals of Antimicrobial Therapy ▪ Cure the patient’s infection ▪ Limit harm by minimizing patient risk for adverse effects, including secondary infections ▪ Limit societal risk from antimicrobial-resistant bacteria  ETIOLOGY OF INFECTIONS ▪ Nosocomial ▪ Community acquired infections   PATHOPHYSIOLOGY Endogenous infection- arise from alteration in Exogenous Infections- acquired from an one’s own normal flora external source ▪ Recent antimicrobial use may allow for ▪ Human-to-human transmission overgrowth of other normal flora ▪ Contact with exogenous bacterial ▪ Disruption of host defenses (eg: populations in the environment immunocompromise) ▪ Animal contact. What is the difference between virulence and resistance?  NORMAL FLORA  CLINICAL  PRESENTATION AND DIAGNOSIS ▪ Physical Examination: Fever ▪ Imaging Studies- To determine anatomic localization of infection Radiographs, CT, MRI ▪ Non-microbiologic Laboratory Studies: WBC, ESR, CRP ▪ Microbiologic Studies Culture- Direct examination of specimen eg: sputum, blood, urine Bacterial cultures should be obtained prior to initiating antimicrobial therapy- WHY?   FEVER ▪ Fever- A rise in temperature arising as part of the overall host response to microbial toxins. It is a non-specific sign Fever may also be caused by: ▪ Medications (eg: penicillins, ??, ??), ▪ Trauma ▪ Other medical conditions eg, autoimmune disease, malignancy, pulmonary embolism and hyperthyroidism   ▪ Some patients with infections may present with hypothermia (eg, patients with overwhelming infection). ▪ Elderly patients may be afebrile ▪ Patients with localized infections (eg, UTIs) may also be afebrile.  SUMMARY OF CLINICAL PRESENTATION  TREATMENT  Considerations for selecting antimicrobial regimens Drug specific Patient specific Spectrum of activity Anatomic location of infection Dosing Antimicrobial history Pharmacokinetic properties Drug allergy history Pharmacodynamic properties Renal and hepatic function/Age Adverse effect potential Concomitant medications Drug-interaction potential Pregnancy or lactation Cost Compliance potential   OUTCOME EVALUATION ▪ Patient education- What should go into patient education? ▪ De-escalation of antimicrobial therapy based on culture results ▪ Discontinuation of antibiotics that are providing a spectrum of activity greater than necessary to treat the infection ▪ Discontinuation of duplicative spectrum antibiotics ▪ Switching to a narrower spectrum antibiotic once a patient is clinically stable. ▪ Switch from IV (which is more expensive) to oral   MONITORING ▪ Monitor for clinical response and adverse effects ▪ Efficacy- vital signs, clinical findings, physical exam findings ▪ Toxicity- Adverse effects ▪ Imaging- Repeat diagnostic testing as needed ▪ Lab data- WBC, follow up on C/S tests   Failure of Antimicrobial Therapy Causes ▪ Consider alternative non-infectious diagnosis. ▪ Inadequate diagnosis resulting in poor initial ▪ Reevaluate for sources of untreated infection. antimicrobial or other non-antibiotic drug selection ▪ Perform source control ▪ Poor source control ▪ Consider other drug- and patient-specific factors: appropriate dosing, patient compliance, and drug interactions. ▪ Development of a new infection with a resistant ▪ Physical exam findings organism ▪ Monitoring of therapy ▪ Change antimicrobial therapy based upon findings. What is source control? PHARMACOTHERAPY OF SKIN INFECTIONS Thelma Ohene-Agyei PhD Dept of Pharmacy Practice & Clinical Pharmacy University of Ghana Outline Bacterial Skin Infections – Boils, Buruli ulcer Fungal Skin infections- Candidiasis, Ringworm Viral Skin infections- Herpes, chicken pox ANATOMY OF THE SKIN PHYSIOLOGY OF THE SKIN Identity/ Commubication of emotion/health Protection Thermoregulation Immunology Synthesis: Melanin, Hormones, Vitamin D  BACTERIAL SKIN INFECTIONS Majority of caused by the gram-positive bacteria Staphylococcus and Streptococcus spp. Empiric antibiotic therapy. Current recommendations include penicillinase-resistant penicillins, first-generation cephalosporins, azithromycin, clarithromycin, amoxicillin-clavulanic acid, or a second- generation fluoroquinolone. Gram-negative coverage with a second-, third-, or fourth-generation cephalosporin is usually indicated in children under three years and in patients with diabetes or who are immunocompromised.  A boil (furuncle) is a deep inflammatory nodule developing from a preceding folliculitis (inflammation of the follicles). It begins as a firm, tender, erythematous nodule that BOILS becomes fluctuant and painful and commonly ruptures spontaneously with drainage of pus. Commonly seen on the face, axillae and buttocks Investigations: FBC, FBS (if diabetes is suspected) Sensitivity testing for recurring infection  To treat infection Treatment To relieve pain objectives To identify underlying condition To prevent complication eg: scars & keloids  INTERVENTIONS Pharmacological Non pharmacological Flucloxacillin Incision & drainage of pus Erythromycin (1st line) and Wound dressing clarithromycin (2nd line) are first- for patients with penicillin allergy  BURULI ULCER BU is a necrotizing skin infection caused by Mycobacterium ulcerans. 3rd most important mycobacterial disease globally in immune competent individuals. The lack of pain associated with BU disease usually results in seeking medical treatment late which easily leads to complications. The current existing control strategy is early case detection  Epidemiology Not entirely known, due to Focal distribution of cases Late reporting of cases Lack of health facilities including laboratory expertise and infrastructure for case confirmation in endemic countries of Africa. Currently reported in 33 countries, with the greatest disease burden in West Africa. Commonly found in populations living near rivers, swamps, and wetlands In Ghana, 1993-1998: ~1200 cases. 2004-2014: >9000 cases  CLINICAL PRESENTATION CATE- Characteristics GORY Variable clinical presentation based on geography; 1 single lesion < 5 cm in diameter In the Pacific regions BU may start as a papule. In West and Central Africa it may start as a 2 single lesion 5–15 cm in diameter painless nodule without the involvement of subcutaneous tissues 3 single lesion >15 cm in diameter, multiple lesions, critical sites, and Lack of pain osteomyelitis Nodule gradually erodes leaving a well- demarcated ulcer with wide undermined edges Investigations Treatment Objectives Wound swab for AFBs, C&S To limit extent of tissue destruction Skin biopsy for Histopathology To prevent disability To treat bacterial infection (1o & 2o)  Rifampicin PO and IM streptomycin/ Clarithromycin PO Treatment Surgery as an adjunct for improving wound healing and correction of deformities.  Widespread & although not life-threatening can cause morbidity Common in skin, hair & nails FUNGAL SKIN Increased prevalence due to: INFECTIONS Worldwide travel High numbers of immunocompromised patients Growing use of broadspectrum antibiotics  Aetiology Dermatophyte fungi (Trichophyton, Microsporum and Epidermophyton species). generally responsible for infections of keratinous tissue: the skin, hair and nails. “Tinea” Yeasts (Malassezia furfur and Candida). Typically affect the mucous membranes, but may also be responsible for infection of the skin and nails. Investigations Treatment Goals Microscopy Eradicate infection Culture Prevent transmission FBS & HIV status Prevent complications & sequale Identify & treat predisposing or underlying conditions  General principles of treatment Topical Therapy First line treatment is with topical agents. Why? Principal side-effects of topical agents are local irritation and sensitivity reactions. Treatment is generally required for four to six weeks to effect a cure and may need to be continued beyond the resolution of symptoms  Oral therapy Chronic infections Extensive or disabling disease Immunocompromised patients Patients unresponsive or intolerant or topical treatment Infection Signs & Symptoms Treatment Tinea captis Head & Scalp: Oral Therapy Scaly patches on the scalp 1st Line: Griseofulvin Hair loss 2nd Line: Terbinafine (not recommended in adults) Tinea corporis Trunk & Extremeties Topical: Round lesions, scaly patches that have a well defined, 1st Line: Benzoic acid/ enlarging border and a relatively clear central portion. Clotrimazole/ Miconazole May or may not itch 2nd Line: Griseofulvin/ Iatraconazole/ Terbinafine Tinea pedis Affects feet, usually related to sweating and warmth, and Topical anti fungal creams or use of occlusive footwear. ointments Men between 20 and 40 years. Itraconazole > terbinafine > Griseofulvin > Fluconazole White, macerated areas in the 3rd or 4th toe webs. Itching  Candidiasis Candida albicans: cause infections particularly in warm and moist areas of the body Factors associated with increased colonization rates of C. albicans Broad-spectrum antibiotics. Why? Diabetes mellitus Systemic corticosteroid treatment Hematological malignancies and solid tumors Severe traumas and burns Premature birth  Epidemiology 3 of every 4 women have at least one bout of vulvovaginal candidiasis in their lifetime. More than 90% of HIV positive patients experience oropharyngeal candidiasis and 10% have at least one episode of oesophageal candidiasis. Candidal colonization is at the highest levels during the extremes of ages, in neonates and people older than 65 years  Infection Signs & Symptoms Treatment Oropharyngeal Asymptomatic, sore, and painful mouth, burning mouth or Topical (nystatin, clotrimazole, candidasis tongue, dysphagia, whitish thick patches on the mouth, miconazole, amphotericin B oral tongue, gums. suspension) o Presence of retrosternal pain, epigastric pain, nausea, and vomiting may suggest oesophageal candidiasis. systemic oral azoles (fluconazole, itraconazole, ketoconazole). Vulvovaginal Vulvar pruritus, vaginal discharge, dysuria, and dyspareunia. Fluconazole 150mg P.O./ candidiasis The vagina and labia are erythematous, with a thick curd like Clotrimazole/ Miconazole discharge. pessaries Clotrimazole cream Candida balanitis acquired through sexual intercourse with a partner who has ?? vulvovaginal candidiasis. A patch resembling thrush appears on the glans and may spread to the thighs, gluteal folds, buttocks, and scrotum Non-Pharmacological Interventions Good personal hygiene Wear loose clothing & open footwear Boost immune system VIRAL INFECTIONS  CHICKEN POX Highly contagious disease of child hood or (adult that has never had chicken pox) Aetiology: Varicella zoster Mode of transmission The disease is transmitted through inhalation of infective droplet nuclei Incubation period Contact with lesions after 10-20 days. Clinical Manifestation Complications Fever and malaise are usually mild in Secondary bacterial infection particularly children and more severe in adult with group A beta hemolytic streptococci Pruritic rash most prominent on the Encephalitis (rarely) face, scalp and trunk Cellulites, osteomyelitis, epiglottis’s and Vesicular lesion, quickly rupturing to pneumonia are more common in adults form small ulcers and appear first in oropharynx But in children acute respiratory disease syndrome is the common complication  Treatment objectives Investigations To relieve itching & pain Clinical diagnosis To prevent secondary infection PCR or cell culture of body fluids To prevent dehydration (especially in children) Pharmacological intervention Non-pharmacological Paracetamol (Pain relief) interventions Keep skin clean Soothe skin & relieve itching High fluid intake Calamine lotion/cream Cetirizine/Promethazine/Chlorphenira Isolation mine Bed rest Antiviral (which immune status?) Maintain nutritional status Aciclovir Why shouldn’t you scratch vigorously? 2o bacterial infection Fluclox/Amoxiclav Azithromycin PHARMACOTHERAPY OF STIs THELMA OHENE-AGYEI, PHD DEPT OF PHARMACY PRACTICE & CLINICAL PHARMACY UNIVERSITY OF GHANA, LEGON  STIs: WHAT ARE THEY? Infections that are transmitted from person to person through sexual contact Causative organisms are transmitted through blood, semen, vaginal or other body fluids Common STIs: ?? Non-sexual transfer can occur through: ??  STIs IN PREGNANCY Early labour Stillbirth Complicated delivery Easily transmitted from mother to child: During pregnancy Childbirth After baby is born Effects on baby include: Low birth weight Neurologic problems Eye infection, blindness ? ?  HIV/AIDS Human Immunodeficiency virus (HIV) A retrovirus with a strong affinity for CD4 receptor protein found predominantly on cells of immune system (eg:…?) Over time chronic infection deplete these cells leaving body susceptible to infections and tumors. This progressive deterioration in cellular immune response that leads to symptomatic disease and Acquired Immune Deficiency Syndrome (AIDS) TRANSMISSION OF HIV  GLOBAL AIDS STATISTICS Prevalence is 0.7% among adults 39 m people living with AIDS (1.5m are children) 2/3 of PLWHA live in Africa 630K people died of HIV related illnesses 85% are aware of their status 75% are accessing treatment 92% have viral suppression GHANA AIDS STATISTICS Adult prevalence is 1.6% >354,000 people living with AIDS 67% are women 8% are children