Role of the Pharmacist - Education to those at risk

• Advocate for vaccines • Watch for trends • Warn those exposed to Zika • Educate the public (risk of infection/transmission) • Protect those who are traveling • Show the old ladies where the Q-tips can be found within the store

Emerging Infectious Diseases

Infection Causative Agents What about it Tx Imagine Ebola A filovirus:

ebolavirus (EBV) • (ssRNA)

Blood all over We havn’t had enough time/cases to test our new therapies

Supportive Therapy Whole Blood Transfusions Vaccine: ZEBIV has shown some promise ZMapp – potential mAb option

Richard Preston’s The Hot Zone – scene where the guy’s innards liquefy and he bleeds out like a Rum Cordial

Zika A flavivirus:Zika Virus (ZIKV) • (ssRNA)

Not that big of a deal unless you’re tryna baby-make If you visit an endemic area, just use the barrier method for a while after.

Prophy: DEET + Barrier method - Men – 24weeks - Women – 8 weeks (talking barrier method)

Tx: Supportive. It is self-limiting

A pregnant woman on a safari

Legionnaire’s Disease

Legionella spp Primarily L. pneumophila

Transmits by aspiration. Skip going to the American legion for fish frys for a few years.

Tx: FQ or Azithro Old men at the American legion smokin’ death sticks

(4/18) Bulman Lecture: Osteomyelitis/Diabetic Foot Infections Classifying Osteomyelitis: Inflammation of the bone caused by an infection. Characterized by pain and loss of function

1. Hematogenous Osteomyelitis: Bacteria in the blood get trapped in the bone a. Vertebral Osteomyelitis (adults > adolescents)

2. Osteomyelitis due to Contiguous Infection: When the site of infection is adjacent to the bone – direct access a. Posttraumatic/Secondary to Fracture

3. Osteomyelitis due to Vascular Insufficiency a. Diabetic foot infections

Pathophysiology Normal bone is highly resistant to infection when the outer cortical bone is intact. Trauma to the cortical bone greatly increases the risk of infection. Development of osteomyelitis is often the result of: • High inoculum of bacteria • Trauma to the cortical bone • Placement of foreign bodies Hematogenous Osteomyelitis is most often monomicrobial Osteomyelitis due to Contiguous infection is typically polymicrobial Osteomyelitis secondary to fracture or diabetes mellitus is typically polymicrobial

Bacterial Adhesins: Bacteria, such as Staph aureus, express adhesins to bind to and grow within bones - Infective bacteria can adapt to the bones, leading to persistence and high-recurrence rates if treated

for short-duration Bacterial Growth: Growth within bones will produce pus and pressure. This may result in bone necrosis (sequestra) followed by new bone formation - Acute Osteomyelitis: Refers to bone infections where necrosis has not yet occurred - Chronic Osteomyelitis: Bone necrosis has occurred. This is often >3mo since initial infection

Common Pathogens à Staph aureus ß Staph is the predominant infective pathogen in osteomyelitis due to their adhesion virulent factors. Additionally, the ability to form biofilms promotes resistance to treatment. MRSA is on the rise.

- Other infective pathogens: Streptococcus spp, Gram(-) Bacilli, P. aeruginosa, Anaerobes Clinical Presentation and Diagnosis

- S/Sx: Gradual onset of localized pain, tenderness, warmth, erythema, and swelling. Pus is generally restricted to the more series infections or diabetic foot infections.

- Dx: Patients at higher risk of osteomyelitis should be examined o PE: Local vs Systemic signs of inflammation o Probe-to-Bone Test: Diagnostic technique applied to open wounds used to exclude osteomyelitis

• (-) = Can’t touch bone: Exclude osteomyelitis, treat for ABSSSI • (+) = Suspect osteomyelitis, perform radiographic imaging/biopsy to confirm

o Radiologic Tests: X-Ray o Bone Biopsy: The gold-standard. Biopsy of bone with bacterial growth/histological findings of

necrosis/inflammation. Treatment Approachà • Determine the need for surgery • Select abx therapy • Select duration of abx tx Determining the need for surgery

- Decision: Depends on the severity of infection, presence of hardware, and efficacy of antibiotics • Chronic Infections (>3mo): Surgery is almost always required to remove the sequestrum • Necrotic Tissue: Surgical debridement of necrotic tissue is often required. Additionally, efforts to re-vascularize the patients with poor blood-flow to the infected extremity should be considered (diabetic foot infections)

- Surgery/Amputation: In rare and severe cases, removal of bone is required. Selecting Antibiotic Therapy

à Get cultures before initiating treatment If known, abx therapy should target cultures/susceptibility - Patient Status

o Unstable Patient: In absence of culture data, treat empirically. (Unstable ~ BP, HR, RR, etc) o Stable Patient: Wait for bone biopsy culture and sensitivity results before beginning treatment

- Abx PK/PD Considerations o Penetration: Will the abx penetrate the bone, is a particular dose necessary to penetrate the bone

§ AG have poor bone penetration. Avoid AG (amikacin, gentamicin, kanamycin, etc) o IVàPO: Drugs with bioavailability should be given PO when indicated.

§ b-lactams have poor bioavailability and should not be administered orally o Duration of Therapy: Abx tx will last at least 6 weeks, consider the AE of abx over that course of time

§ Linezolid has laudable bone penetration, but high risks of anemia and thrombocytopenia (avoid) - Empiric Therapy

o Generally, empiric therapy is reserved for hemodynamically unstable patients. Therapy should cover: § MRSA, Streptococci spp, Gram(-) bacilli

à Vancomycin + Cefepime à PCN-ALL: Vanco + Cipro/Aztreonam

- Directed Abx Therapy Staphylococcus aureus MSSA: à Nafcillin/Oxacillin 2g IV q4º or continuous -OR- Cefazolin 2g IV q8º à PO Option: Bactrim 1 DS PO q12º + Rifampin 600mg PO q24º MSSA Severe PCN-ALL: à Vancomycin 15-20mg/kg IV q12º MRSA + Coag(-) Staph: à Vancomycin 15-20mg/kg IV q12º -OR- Bactrim 1DS PO q12º + RIF

Staph Adjunctive therapy – Rifampin (RIF) o Shown to act synergistically with bactericidal activity against biofilms o RIF is indicated for combination treatment of staphylococcal osteo in cases of:

• Prosthetic joints • PO therapy is required *There is little evidence supporting its use. The decision to use it should consider drug-interactions and hepatotoxicity

Streptococcus spp. PCN-Sensitive: à Ceftriaxone 2g IV q24º -OR- PCN G IV q6º or continuously PCN-ALL: à Vancomycin 15-20mg/kg q12º PCN-Resistant: Depends on susceptibility. à Ceftriaxone if susceptible, otherwise à Vancomycin Pseudomonas aeruginosa + Enterics (E. coli, K. pneumoniae, Enterobacter, Citrobacter, etc)

à Cefepime 2g IVq12º -OR- Meropenem 1g IV q8º PO: Cipro 750mg q12º o How to choose?

§ Need to cover ESBLs? à Meropenem would be chosen. PCN ALL à Cipro § Want to do PO à Cipro is our only good PO option for pseudomonas

Salmonella spp. à Cipro 500mg PO q12º -OR- Ceftriaxone 2g IV q24º

o Sickle cell patients presenting with Osteomyelitis are most commonly (50%) infected with Salmonella

“Do not need to know doses for the exam”

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Special case: Vertebral Osteomyelitis [8 weeks tx] - Pathogen: Staph aureus (50%) - Vertebral osteomyelitis is most often caused by hematogenous spread. Patients present with acute worsening back

pain often localized to one location and the other typical signs of infection (TÝ, CBCÝ) - Risk Factors generally relate to the promotion of bacteremic infections: IVDA, Hemodialysis, Immunocomp

Special Case: Posttraumatic Osteomyelitis/Compound Fracture - Pathogens: Staphy and Gram(-) Bacilli are the most common, stemming from skin/soil/hospital flora - Tx: Irrigation + debridement + Abx prophylaxis within 6 hours of open trauma to reduce osteomyelitis risk

à Vancomycin + Cefepime/Aztreonam for 1-3 days post-trauma. Avoid FQ – Reduced fracture healing Duration of Therapy Osteomyelitis Tx continued

- Due to the presence of bacterial biofilms, difficulty of bone penetration and bacterial persistence, prolonged therapy is recommended. A minimum of 6 weeks is recommended in most patients

- IVàPO: This decision should be made for all patients, except when using b-lactams due to poor bioavailability - Exceptions: Vertebral osteomyelitis has a high rate of recurrence, identify risk factors for treatment duration

o Risk Factors: (1) Paravertebral abscess, (2) MRSA infection o Low Risk = No risk factors: 6-8 weeks treatment o High Risk = ³ 1 risk factor: ³8 weeks treatment

Diabetic Foot Infections (an ABSSSI ± Osteo) - 15-25% of DM patients will develop a foot ulcer. Studies suggest that high glucose levels lead to impairment of

neutrophils which puts patients at higher risk for infection. Not all foot ulcers are infected. It is important to understand how to identify an infected ulcer and the risk factors predisposing infection

- True Diabetic Foot Infection o Pathogen: Gram(+) cocci, especially Staph o Dx: At least 2 of the following Sx:

Local swelling Erythema Local tenderness/pain Local warmth Purulent discharge § Severity of the infection depends on the size and depth of infection, as well as systemic sx § At-Risk: Concurrent peripheral neuropathy, peripheral arterial disease, immunocompromised

- Empiric Treatment: IDSA Guidelines suggest treating empirically based on severity Regardless of the diagnosed severity of the foot infection, if a risk factor for MRSA or Pseudomonas is present, it will need to be covered for

n Mild Target: MSSA + Streptococcus spp à Cephalexin -OR- Augmentin

n Moderate Target: MSSA + Streptococcus spp + Enterics + Anaerobes à Augmentin -OR- Unasyn -OR- PipTazo

n Severe Target: MRSA + Pseudomonas + Streptococcus spp + Enterics + Anaerobes à Vancomycin + Cefepime + Metronidazole

- Targeted Treatment: Appropriately conducted wound cultures may be used to narrow antimicrobial therapy o Good Culture: Aspirate from abscess, OR, deep tissue scraping. Don’t let some noob just superficial swab o Avoid Treating Coagulase negative staphylococci and enterococci – they have a low virulence and are

most likely a contaminant. - Duration of Treatment: Until the infection has cleared! ~ Mild: 1-2w Moderate to severe: 2-3w

o Switch IVàPO when the patient’s infection has responded to the regimen o Treat longer in patients with osteomyelitis in the setting of a diabetic foot infection (6w)

- If the patient is worsening despite being treated empirically, broaden and intensify the regimen. A possible complication of diabetic foot infections is osteomyelitis, especially for deep chronic ulcers near bones.

o à Use a probe-to-bone test to help diagnose and perform an MRI with bone biopsy to confirm o Targeted treatment for osteomyelitis secondary to diabetic foot infection should extend for ³ 4 weeks. If

the bone was resected, 1 week is sufficient One critical point, the wound care we learned in PHAR 501 is not going to prepare us for diabetic foot infections. Call up the wound care specialist to get some quality cultures, nice wraps, and clean irrigation and debridement

+MRSA Coverage Cephalexin PO + Bactrim PO

+Pseudomonal Coverage Cephalexin PO + Cipro PO

+MRSA Coverage Unasyn IV + Vanco IV

+Pseudomonal Coverage Choose PipTazo

Infection Vertebral Osteomyelitis Posttraumatic Osteomyelitis Diabetic Foot Infection Infective Agent

Staphylococcus aureus None, this is prophylactic tx post-injury Common: Staph, Gram(-) bacilli

Gram(+) cocci, often Staph

Empiric Tx

Typically empiric treatment is not required. Wait for cultures and sensitivities Hemodynamically unstable? Ok fine à Vanco + Cefepime/Aztreonam

Prophylaxis (within 6 hours) Ø Vanco + Cefepime

Severe PCN allergy – use Aztreonam

• Mild: Cephalexin PO or Augmentin PO • Moderate: Augmentin PO or Unasyn IV • Severe: Vanco +Cefepime+Metronidazole Anti-pseudomonals: Cipro, PipTazo Anti-MRSA: Bactrim, Vanco

Duration of Tx

Minimum 6 weeks ³8 weeks if high risk of recurrence (MRSA or vertebral abscess)

1-3 days post-trauma 1-3w based on severity

(4/20) Max Lecture: HIV: 30 years and still counting – Part I In 1981, the first reports emerged telling of complications related to a newly spreading virus, HIV, in otherwise healthy white MSM populations. By 1982, the term AIDS was coined by the CDC. In 1985, HIV was confirmed to cause AIDS HIV

- Epidemiology: 1.2million infected in the US, 75% are male. 2018 is the first year where the incident rate of HIV infections has gone down. AA comprise the majority of the newer infections. Africa has the most HIV pts

o Nevertheless, all races are equally affected, HIV/AIDS knows no color. o Mortality: Trends in mortality were continually on the rise up until 1995, whereupon the advent of

combination therapy came about, greatly decreasing the mortality rate. Between the years 1991-95, the most likely cause of death for the 25-44yo cohort was AIDS related complications!

- Pathophysiology: HIV is a virus o Upon exposure, the immune system develops antibodies to help fight the infection. However, HIV

replication is prolific, producing 1 trillion (10^12) virions daily. The antibodies are therefore not protective, and the immune system becomes overwhelmed. The highly variable genetic diversity exhibited by the virus is due to a lack of proofreading mechanisms, which prevents successful protection by antibodies and vaccine development. The virus does not kill people, it only kills the immune system.

- Dx o HIV(+): Two-series standard antibody test. The first is to identify and the second is to confirm

§ 1: Sensitivity § 2: Specificity

o AIDS = HIV(+) and CD4 T-Cell count < 200cells/mL or HIV(+) with one or more AIDS defining illness § Rationale for 1st Dx: The opportunistic infections generally start emerging when T Cell < 200, so

these patients are at risk. However, if already infected with one, it is suitable criteria to dx AIDS § Opportunistic Infections: Candidiasis (esoph, bronch, trach, pulm), invasive cervical cancer,

coccidiodomycosis, cryptococcal infection (meningitis), Herpes Simplex, MTB, recurrent pneumonia, wasting syndrome due to HIV, toxicoplasmosis encephalitis • Pneumocystis carinii (jiroveci) pneumonia (PCP/PJP) is most common (30%) for AIDS Dx

- Risk factors for Transmission: MSM, IVDA, Heterosexual contact, needle sticks, vertical transmission, blood transfusions [Transfusion: ~93%, Vertical w/o tx: ~25%, MSM ~1.5%, IVDA ~0.6%, the rest are lower)

- Transmission: Contact with infected bodily fluids. Fluids include: Blood, semen, vaginal fluids, breast milk o NOT BY kissing, sweat/tears, sharing utensils, toilet seats, insects o Ryan White (hemophiliac infected via blood transfusions): Instrumental in educating the public on this

taboo disease. He taught how it was not transmitted – normal everyday contact will not transmit. o Infectivity depends upon (1) Size of the viral load, (2) Presence of STDs – they travel together

- Preventative Measures o Screening: The CDC recommends HIV screening for all people 13-64yo. It is estimated that 13% of the

population does not know that they are infected. o Get-linked to care: For those people who do get diagnosed, only 66% are linked to care. As a result, they

will not achieve viral suppression – and thus remain contagious. - Adherence to anti-retroviral HIV therapies (Life-long dx à life-long tx)

o Primary reason for HIV tx failure is suboptimal adherence Once treatment begins, it should not be interrupted unless severe ADR Stern counseling and education is critical. Achieve understanding on the AE and commitment

o Poor Clinic Follow-up: Here is our role as pharmacist and how we can impact their therapy. It is critical to assess medication adherence at every visit

Standard Ab tests: ELISA + WB or multispot

Predictors of Poor Adherence Poor clinic follow-up Lack of education about HIV Psychosocial (denial, anxiety) Boozer, IVDA Pill burden [eliminated] Side effects of drugs Unstable living (homeless)