The final exam will cover all lectures with a strong emphasis on material presented in the latter half of the quarter. Much of the final exam is in a case-based format and will consist of approximately 60 multiple choice and matching questions. As a general rule, you will be presented with a patient with a specific infectious disease, which you may need to identify based on signs/symptoms/Gram stain results. Questions regarding the disease state/syndrome, treatment recommendations, and issues specifically relating to antimicrobial therapy will be asked.

As you prepare for the exam, be able to identify the causative organism for each particular disease state (consider resistance issues) and understand how the infection presents clinically (complicated vs. uncomplicated). Based on this information and characteristics specific to the patient (renal dysfunction, allergies, liver dysfunction) be able to make appropriate treatment recommendations. Also, be aware of adverse drug reactions that can be caused by your treatment recommendations.

This study guide is NOT intended to replace your notes, readings, lecture handouts. The purpose of this study guide is to assist you in focusing your studying efforts only.

These study objectives cover material presented in the second half of the course

ENDOCARDITIS

Acute vs. subacute endocarditis

Risk factors for endocarditis
    congenital heart disease
    IV drug abuser
    valve prosthesis
    mitral valve prolapse with regurgitation
    valvular stenosis and regurgitation
    rheumatic heart disease
    indwelling intravascular devices- central venous catheters

Pathophysiology

    Surface alteration -->NBTE --> Bacterial attachement -->sheath cover

Etiology  
    Mostly gram positive infection
    Depends on native vs. prosthetic valves
    Streptococcus
    Enterococcus
    S.aureus and S. epidermidis

Valves effected  
    Right vs. left sided

Clinical Presentation
    Vauge presentation
    Janeway lesions, Osler nodes, Splinter hemorrhages, petechiae, 
    roth spots

Laboratory findings
    X3  Blood cultures
    Transthoracic echo (TTE) vs. Transesophageal (TEE)
   

Treatment
    Surgical: valve replacement
    Drug therapy based on native vs. prosthetic valve
    Staphylococcus
        Nafcillin (4 to 6 weeks) PLUS gentamicin (3 to 5 days)
        MRSA: substitute nafcillin with vancomycin
        Prosthesis: Nafcillin PLUS Rifampin (6 weeks) PLUS gent (2 wks)
    Streptococcus
        Penicillin G (2-4weeks) with gentamicin (2 weeks)
        PCN allergic: substitute PCN G with Cefazolin or vancomycin
    Enterococcus
        Ampicillin plus gentamicin (4-6 weeks)
        PCN allergic substitute ampicillin with vancomycin
    Be aware of Bacterial resistance issues
    Drug concentrations
        gentamicin low dose: peak of 3 - 5 mg/L

Understand what patients are at risk and who to prophylaxis.

SKIN & SOFT TISSUE INFECTIONS

Understand basic definitions and skin composition.

Normal Human Host Defenses to Bacterial Colonization
    Limited epithelial cell adherence by pathogens
    Intact stratum corneum
    Low skin pH
    Host immune system
    Resident skin flora

Resident Human Cutaneous Flora
    Gram positive cocci (S. epidermidis 50%)
    Gram positive bacilli
    Gram negative bacilli
    Fungi

Impetigo & Ecthyma
    Impetigo: golden "stuck on" crusts around mouth/nostrils
    Ecthyma: "punched out" ulcers deeper into dermis on lower     
    extremities
    Etiology: Group A streptococcus
    Tx: PCN G IM; PCN VK P0; macrolide if PCN allergic.

Carbuncle & Furuncle
    Furuncle: acute inflammation of skin, gland, hair follicles
    Carbuncle: more extensive and multiple
    Etiology: S. aureus
    Tx: moist heat for localization/drainage
    Keflex, Ceclor, Cefzil P0
    Nafcillin or Ancef IV
    Clinda or macrolide for PCN allergic
    Clean clothing, bedding, towels, and general skin care for 
    prophylaxis

Erysipelas
    Red rash on bridge of nose/cheeks & systemic symptoms
    Etiology: Group A streptococcus (rare S. aureus)
    Tx: PCN G IM; PCN VK P0; macrolide if PCN allergic

Cellulitis
    Due to previous trauma or skin lesion
    Acute and can spread rapidly.. .can be very serious
    Etiology: S. aureus and S. pyogenes
    Tx: immobilization and elevation; moist heat; cool dressings 
        Monitor for compartment syndrome (surgical intervention 
        required) 
        Keflex, Ceclor, Cefzil P0
        Nafcillin or Ancef IV
        Clinda or macrolide for PCN allergic
        Nafcillin + Gent; Clinda + Cipro: or Vanco for high-risk patients
        Vanco for MRSA

Crepitant Cellulitis & Necrotizing Cellulitis
    Minimal clinical findings (local pain and erythema)
    Limb- and life-threatening condition (aggressive therapy)
    Necrotizing: S. pyo genes
        Bullae with red-black fluid for necrotizing (1-3 days
    Crepitant: Clostridium perfingens
        Gas production and foul smelling discharge for crepitant
    Tx: surgical intervention warranted (debridement)
        IV therapy only

Bite Wounds
    Two classes of presentation (<l2hr and >l2hr)
    Dog/cat - Pasturella multocida
    Human - Eikenella corrodens
    Tx: Copious irrigation of wound
    Consider surgical debridement and exploration for hand wounds
    Tetanus immunization
    Augmentin P0; Unasyn IV; Ceftin, Clinda, Doxy, Levo for PCN 
    allergic

Burn Wounds
    Significant disruption of homeostasis (oxygen, nutrients, and cells 
    to wound)
    Biopsy is important for diagnosis and prognosis
    Etiology: MRSA and others (fungi, yeast, Gram negatives)
    Tx. Vanco (aggressive tx)

DIABETIC FOOT ULCERS & OSTEOMYELITIS

Diabetic foot ulcers
    Extension of cellulitis with diabetics
    Always consider degree of renal impairment
    Mild vs. moderate-severe vs. severe
    Etiology: 
        Polymicrobial (3-5 organisms on average) 
        Staphylococci and streptococci most common 
        Gram negatives & anaerobes (50%)
    Tx: Empiric P0 and Empiric IV (broad coverage)
    Tx is highly variable based on clinical condition
    Consider factors that can affect antibiotic efficacy

Osteomyelitis
    Differential between hematogenous vs. secondary vs. vascular 
    insufficiency vs. vertebral
    Etiology: S. aureus (50%)
    Varying etiology based on disease state and immune function
    Early diagnosis is critical
    Understand various methods of detection (bone scans, MRI, CT, 
    cultures)
    Tx: nafcillin IV x 4-6 weeks
    Consider surgical intervention (amputation often necessary) 
    Prophylaxis in bone surgery

HIV/AIDS

SEE www.HIVATIS.org for ADULT treatment guidelines

HIV epidemic in South America and Africa

Transmission
    direct inoculation
    sexual transmission 
    mother-to-child
    transplantation

Cellular targets
    CD4 receptor on T_H cells
    Chemokine Receptors - new drug targets

Reservoirs of HIV
    Poor drug penetration into CNS, retina, and testes

Surrogate Markers of HIV
    CD4 counts and 
    viral load counts

Direct relationship between CD4 count and opportunistic infection

Be familiar with HW testing procedures

Be familiar with the natural history of HIV infection, and mortality of HIV disease and the impact of HAART on mortality

Opportunistic Infections
    PCP (pneumoncystic carinii pneumonia) - TMP/SMX; 
    pentamidine; dapsone
    Toxoplasma encephalitis - TMP/SMX
    MAC - clarithromycin or azithromycin or rifabutin
    Candidiasis/Cryptococcus - fluconazole
    Bacterial Infections - GCSF or GMCSF
    Histoplasmosis - Itraconazole
    Cytomegalovirus - ganciclovir

Vaccinations
    pneumococcal; VZV Hib; influenza

4 Pivotal Advances in HIV Tx
    better understanding of replication kinetics
    assay development to determine viral load
    anti-retrovirals with differing mechanisms of action
    combination therapy (superior to monotherapy)

Indications for Antiretroviral Tx Initiation
    see 2001 DHHS Recommendations

Initial Tx Regimen (monotherapv is NOT recommended)
    review chart in notes, understand role of ritonavir
    understand importance of adherence

Nucleoside Reverse Transcriptase Inhibitors (NRTI)
    Zidovudine (ZDV or AZT)
    Didanosine (ddl)
    Zalcitabine (ddC)
    Lamivudine (3TC)
    Stavudine (d4T)
    Abacavir (ABC)

Protease inhibitors (P1) 
    Saquinavir (Invirase® and Fortovase®)
    Indinavir (Crixivan®)
    Ritonavir (Norvir®)
    Nelfinavir (Viracept®)
    Amprenavir (Agenerase®)

Non-nucleoside reverse transcriptase inhibitors (NNRTI)
    Nevirapine (Viramune®)
    Delaviridine (Rescriptor®)
    Efavirenz (Sustiva®)

VIRAL INFECTIONS

Herpes Viruses (HSV)
    Double-stranded DNA viruses
    3 modes of virus interaction
        permissive infection
        latent (restrictive) infection
        malignant transformation

Hallmarks of Herpes Virus Infection
    Ubiquity
    Latency
    Reactivation

Virus Disease State
    HSV-l & HSV-2 labial, genital, neonatal, encephalitis
    VZV chicken pox, zoster (shingles)
    EBV infectious mononucleosis
    CMV retinitis, pneumonitis, hepatitis
    HSV-6 exanthem subitum
    HSV-7
    HSV-8 Kaposis sarcoma

Mode of transmission
    Perinatal and intimate contact; aerosolized transmission by VZV 
    only

Susceptibility   
    not routinely tested in treating viral infections

Acyclovir
    F = 15-30% (IV form has better Cmax values)
    Vd = 50L
    Renal elimination (renal dosing required)
    Hepatic metabolism (8-14%)
    Act as prodrugs (need activation)
    Mechanism of action - Obligate chain termination (require active 
    DNA replication to work)
    Topical acyclovir is typically not used clinically
    VZV dosing - 8OOmg Sx/day P0 (Cmax = 7.5 and Cmin = 3)

Clinical Presentation of Herpes Virus Infections
    Localized infection (genital, non-genital, perianal/anal, orolabial)
    CNS (encephalitis, meningitis)
    Visceral dissemination (esophogus, intestines, lower resp tract, 
    liver, pancreas)

CDC Recommendations for Tx of Genital Herpes
    Genital or mucocutaneous HSV does not mandate tx
    Treatment is highly individualize

HSV Infections Requiring Tx
    Mucocutaneous HSV in immunocompromised host
    Recurrent HSV in in immunocompromised host
    Herpes encephalitis
    Neonatal herpes

Varicella-Zoster Virus (VZV)
    Vaccination is key but many issues remain unresolved
    Primarily a childhood disease (more complicated in adults)
    Chicken pox
    Shingles
    Ophthalmicus (requires aggressive tx)
    Typically, no tx required for children with chicken pox
    Valacyclovir or famcyclovir good options for VZV

Cytomegalovirus (CMV)
    True opportunistic pathogen (requires immunocompromised host)
    CMV syndrome vs. invasive disease
    CMV Retinitis
        common in ADS patients
        Leads to irreversible blindness
        Becoming less frequent
    CMV Pneumonitits
        common in BMT patients
        17% incidence following allogeneic transplans
        85% mortality rate (untreated
        Associated with GVHD
        Onset median = 62 days post transplant
        Ganciclovir is tx of choice (foscarnet has slight HIV activity)
    Intraocular ganciclovir insert for CMV retinitis prophylaxis

INFECTIOUS DIARRHEA

Common Foodborne Pathogens: Campylobacter/ E. coli O157:H7/ Listeria monocytogenes/ Salmonella/Shigella / Parasites/ Viruses

Treatment options

SURGICAL PROPHYLAXIS

Prophylaxis vs. Wound Infections

Factors influencing the incidence of infection following surgery

Be able to describe classification of surgical procedure and based drug therapy on this classification:
    Clean: S. aureus, S. epidermidis - Cefazolin
    Clean-contaminated: S. aureus, streptococci, oral anaerobes
    Cefazolin
    Contaminated: polymicrobial - cefazolin (24-72 hrs)
    Dirty: antibiotics for dirty surgeries is treatment - polymicrobial;     
    cephalosporin (1^st, 2^nd, 3^rd generation )- 5 - 10 days of therapy

Prophylactic antibiotics should be given within 1/2-1 hr of surgery 

INTRAABDOMINAL INFECTIONS

Peritonitis
    Primary, secondary, tertiary, foreign body, aseptic/sterile
    Related to continuous ambulatory peritoneal dialysis (CAPD)

Abscess - 
    Intraperitoneal /visceral

Common causing bacteria: bacteria of the GI tract
    Gram negatives
    Gram positives (enterococci)
    Anaerobes

Clinical presentation: 
    Third spacing fluid, 
    N/V, 
    Fever

Treatment:
    Surgical drainage (other procedures)
    Support vital functions
    Drug therapy: broad coverage
        3^rd generation cephalosporin
        Beta-lactam/beta-lactam inhibitor (i.e. ampicillin/sulbactam)
        Fluoroquinolones
        Metronidazole, clindamycin (anaerobes)

Follow-up:
    Review cultures and tailor therapy

SEXUALLY TRANSMITTED DISEASES

Know and understand the following for chalmydia, gonorrhea, epididymitis, PID, vaginal infections, syphilis, chancroid
        Causing organism
        Clinical presentation
        Treatment options    

Chlamydia
    Etiology: Chlamydia trachomatis (Gram stain, direct antigen test 
    or ELISA)
    NGU vs. gonococcal urethritis
    Majority are asymptomatic
    Treatment: (7days) Doxycycline or Azithromycin
        Alternatives: Ofloxacin, erythromycin, amoxicillin

Gonorrhea
    Etiology: Neisseria gonorrhea, intracellular gram negative diplococci
    Clinical presentation: complicated (disseminated) vs. uncomplicated 
    Infections: urethritis, cervicitis
    Disseminated infection: meningitis, endocarditis, opthalmia 
    neonatorum
    Treatment: based on complicated vs. uncomplicated infection
    ALWAYS ADD ANTI-CHLAMYDIAL REGIMEN
    Uncomplicated (genital infection): ceftriaxone IM x 1 PLUS     
        doxycycline P0 x 7 days
    Complicated (disseminated) : ceftriaxone IV x q24h, switch to oral 
        therapy when patient improves PLUS doxycycline
        

Epidiymitis

    Typically affects men<35 y
    Know causative organisms

Pelvic Inflammatory Disease
    Etiology: POLYMICROBIAL
    Know risk factors
    Clinical presentation: varies, lower abdominal tenderness
    Complications: tubal damage scarring, sepsis, chronic pelvic pain
    Treatment: BROAD COVERAGE, hospitalization may be required
        Cefoxitin/Cefotetan (for broad coverage-anaerobes) PLUS 
        doxycycline
        
   Drugs contraindicated in pregnancy
        Fluoroquinolones, tetracyclines, doxycycline, erythromycin 
        estolate (base OK) and metronidazole (1st trimester)

Vaginal Infections

    Trichomoniasis
    Causative organisms:  Trichomonas vaginalis
    Diagnosis (wet mount); treatment (metronidazole)
    Know whether to treat in pregnancy or not

    Bacterial vaginosis (BV)
    Know etiology, complications, and treatment

Syphilis
    Etiology: T. pallidum (increasing association with HIV infection)
    Clinical presentation: be familiar with stages!!!
    Diagnosis: darkfield exam (early stages), serologic tests (later 
    stages)
    Treatment:
        Drug of Choice: PCN G benzathine for all Stages
        Alternatives: Doxycycline, tetracycline
        Neurosyphilis/pregnant women: PCN is ONLY recommended 
        therapy. If PCN allergy, consider skin test and possible     
        desensitization

Chancroid

    Know causative organism (H. ducreyi)
   PAINFUL lesions
    Azithromycin 1g PO X1 

SEPSIS

Understand the pathophysiology of sepsis, and how the pharmacology of drotrecogin affects the model
Understand the inclusion and exclusion criteria, as well as the results from the PROWESS study and how they relate to the clinical use of drotecogin.
Know the dosing and adverse event profile of drotrecogin

URINARY TRACT INFECTIONS

Epidemiology
    30x more common in women
    Most common etiologies: E coli, S saprophyticus;
    Nursing home/catheterized patients: Pseudomonas spp.,
    enterococcus, yeast, etc. 

Diagnosis criteria
    Urinary analysis (U/A), presence of WBCs, bacteria 10⁵/mL, 
    leukocyte esterase, nitrites, elevated pH

Cystitis/uncomplicated UTI  
    Three-day treatment superior
    TMP/SMX 1 DS BID x 3 days
    May use a quinolone
    Beta-lactams x 5 days
    Pregnant women - amoxicillin x 7 days
    Symptomatic abacteruria - suspect Chlamydia/Neisseria
    Understand contraindications to single dose and 3-day therapy

Pyelonephritis/complicated UTI or uncomplicated UTI
    If the patients is symptomatic, he/she may need to be hospitalized 
    Ampicillin/ ₃rd generation cephalosporin plus aminoglycoside
    Suspect Pseudomonas - ceftazidime/ piperacillin plus 
    aminoglycoside
    Suspect Enterococcus - ampicillin/vancomycin plus 
    aminoglycoside (peaks 3-5 mg/L)

Prostatitis
    protective host factors: high conc. of zinc, antibacterial factor 
    common cause is E coli, Entercocci, Pseudomonas
    treatment similar to pyelonephritis, longer duration 4 to 16 weeks 
    high incidence of treatment failure 30-40%

Recurrent infection
    Understand prophylactic strategies

Catheterized patients
    95% at risk for infection at 30 days
    etiology: E. coli, S. epidermidis, yeast
    Treatment: remove catheter
        antibiotics if systemic infection, treatment 14 to 30 days

UTIs in Pregnancy
    Know antibiotics to use and those to avoid

ASB
    Know definition
    Always treat children and pregnant females

MENINGITIS

Meningitis 
    inflammation of the meninges (membranes) that surround the brain
    generally refers to inflammation often due to infection of 
    subarachnoid space

Common Organisms
    Haemophilus influenzae
    Neisseria meningitidis
    Streptococcus pneumoniae

Identify signs and symptoms: 
    nuchal rigidity, fever, crying/agitation with infants
    Positive Brudzinski's sign
        Flexion of the neck by the examiner produces hip and knee 
        flexion
    Positive Kernig's sign
        Examiner flexes hip at right angle to the trunk and attempts to 
        extend the knee. Contracture or extensor spasm occurs

Interpretation of Laboratory Studies
    CSF values in Healthy Patients and Patients with Bacterial     
    Meningitis

*a normal serum glucose value: 60-100 mg/dL

Pathogen-Specific Characteristics
    Neisseria men ingitidis
        Five serotypes cause meningitis: A, B, C, Y, W-135
        Group B primarily responsible for isolated cases
        Groups A and C primarily associated with epidemics
        Group Y associated with pneumonia; rarely with meningitis
        Petechiae and purpura on presentation can be a primary clue
        Unique immune reaction 10-14 days post onset in spite of tx
    Streptococcus pneumoniae
        Source: approx 50% are due to primary infections (sinusitis, 
        otitis media)
        Case fatality rates are highest in this organism- approach 27%
        Neurologic complications common: seizures and coma
    Haemophilus influenzae
        tiny, gram negative bacilli
        previously, the most common cause of meningitis in children
        Coma and seizures, if present, occur early in course

Advantages and Disadvantages of Steroid Therapy
    Advantage
        Reduces inflammatory reaction
        Reduces neurologic sequelae
    Disadvantages
        GI bleeds
        Antibiotic penetration
        Ischemia

Prevention and Prophylaxis
    Neisseria meningitidis
        Prophylaxis for close contacts of index case is recommended
        Rifampin 600mg PO q12h X 4 doses
    Streptococcus pneumoniae
        Prophylaxis not recommended for general population
    type b
        Prophylaxis of close contacts is recommended when there is an 
        index case and >1 member of the same household is <4 years of 
        age and/or not fully immunized
        Rifampin 600 mg P0 QD X 4 days
        Index case - should also receive prophylaxis prior to discharge