HD1 – Infectious DiseaseIntroduction to Infectious Disease I & II I) Approaches to Clinical Situations A) Approach to patient 1) Symptoms or signs 2) Constellation of findings 3) Consider patient host defenses 4) Is this an infectious disease or something else? 5) Inflammation and distant effects B) Approach to diagnosis 1) Patient history is 90% of the diagnosis 2) Physical exam 3) Tests (a) Gram stain and culture work together to identify pathogenic organisms 4) Empirical treatment if appropriate/necessary 5) Prevention C) Approach to clinical microbiology 1) Draw ≥2 sets of blood cultures (a) Organisms isolated only from broth are often contaminants, which make up 1020% of all positive cultures 2) Organisms have different capacities for infection (colonization) and disease (a) Certain organisms can cause disease in any host (i) Staphylococcus aureus o Treat with βlactams or vancomycin (ii) Group A streptococci (iii) Streptococcus pneumoniae D) Approach to treatment 1) Infectious diseases typically progress slowly, giving the physician time to make the correct diagnosis II) Bayes’ Theorem A) Probability model that can be used to predict disease incidence B) Example 1) Given conditions (a) 1% of women at age 40 who participate in routine screening have breast cancer (b) 80% of women with breast cancer will get positive mammographies (c) 9.6% of women without breast cancer will also get positive mammographies 2) Question (a) If a woman in this age group has a positive mammography at a routine screening, what is the probability that she actually has breast cancer? 3) Solution (a) Assuming a population of 10,000 such women in this age group who all participate in routine screening, 100 of them will have breast cancer (the 1%) (i) 80% of those 100 women will have positive mammographies (b) From the same 10,000 women, the remaining 9,900 will not have breast cancer (i) 950 of them will have positive mammographies (the 9.6%) (c) Thus, the total number of positive mammographies is 1,030 (i) Of these women, however, only 80 of them actually have breast cancer 1 making them particularly susceptible 2) Streptococcus pneumoniae 3) Neisseria meningitidis 4) Haemophilus influenzae 5) Shigella spp. 6) Escherichia coli 7) Rotavirus B) Adolescents 1) Host defenses are typically fine 2) Behavioral risks for infectious disease C) Elderly 1) Innate and adaptive defenses decline IV) Miscellaneous Topics A) Colonization resistance 1) Native flora protect against colonization by a pathogenic organism 2) Major impairment comes from microbial use (a) E..030 positive screens III) Stages of Development and Related Infections A) Infants 1) Lack antibodies of their own until ~5 months of age.000 granulocytes/μL) C) Complement deficiency 1) Increases risk of infection by encapsulated organisms (a) Neisseria meningitidis (b) Streptococcus pneumoniae (c) Haemophilus influenzae (d) Treat these with ceftriaxone D) Asplenia or splenic dysfunction 1) Loss of splenic function increases predisposition to several pathogenic organisms 2) Risk of infection is greatest in the first year and diminishes over time E) Conditions that impair host defenses 1) Malnutrition 2) Diabetes 3) Antibody deficiency F) Rapid empirical treatment is indicated in some scenarios 1) Bacterial meningitis 2) Acute endocarditis 3) Severe sepsis/shock 4) Necrotizing infection 5) Toxic shock syndrome (ii) Approach to Antimicrobial Chemotherapy I) Types of Antimicrobial Therapy A) Prophylaxis 2 .8 liklihood 1.g. Clostridium dificile B) Fever and neutropenia 1) There is a strong qualitative relationship between infection and neutropenia once a threshold has been surpassed (<1.80 cases =7. region. treating subclinical CMV infections in BMT/organ transplant patients C) Empiric therapy 1) Defined as the use of antibiotics in a patient with a suspected infection before the microbiology of the infection is known 2) Microbiology test turnaround can be slower than desired 3) Scenarios in which empiric therapy is used (a) Immunocompromised patients (neutropenia.g.1) E. asplenia.g. least toxic. and Staphylococcus aureus bacteremia B) Broad to narrow spectrum 1) Based on culture results 2) Based on clinical response C) Discontinuing therapy 1) Clinical course is inconsistent with infection III) Harms of Antimicrobial Therapy A) Related to antimicrobial effect 1) C. endocarditis.) (b) Suspected bacterial meningitis (c) Septic shock (d) Necrotizing infections 4) Choosing empiric therapy (a) Often broadspectrum. etc. difficile colitis 2) Other superinfections 3) Resistance 4) Interference with diagnostic workup B) Adverse drug effects 3 . cheapest. and/or ICU 3) Can consult angiogram if available E) Susceptibilityguided therapy 1) Bestcase scenario. etc. Xaxis represents susceptibility (iii) Gives the percentage of bacterial cases that were susceptible to specific antibiotics D) Pathogendirected therapy 1) The organism is known. CSF in meningitis) may determine whether or not the MIC is interpreted as a resistant/susceptible infection II) Altering Therapy A) Stepping down therapy from IV to PO (by mouth) 1) Patient is clearly improving 2) Gut is healthy 3) Do not step down therapy in cases of meningitis. 3) Susceptibilities are often based on the minimum inhibitor concentration (MIC) (a) Provides the lowest concentration of antibiotic that prevents growth (b) Bacterial location (e. where both organism and susceptibility are known 2) Can streamline therapy based on most effective...g. endocarditis prophylaxis prior to surgery B) Preemptive therapy 1) E. but based on best prediction of microorgansims involved and their susceptibility (b) Antibiogram (i) Generated by hospitals every six months (or a year or so) (ii) Yaxis represents organisms tested onsite. but antibiotic susceptibility is not 2) Must consider likely resistance profiles in that patient. 1) Allergy 2) Toxicity C) Drugdrug interactions 1) Important with drugs that affect CYP450 (e. warfarin) D) IV access complications 1) Clots 2) Infection (local. etc.g.) E) Costs 1) Drug 2) Administration 3) Labs 4 . bloodstream.