Active, Passive Immunity & Antivirals

• Understand safety aspects and education related to prescribing for all drug classes discussed.

Active and Passive Immunity

• Acquired/adaptive immune response is specific, has memory, and takes longer but is more effective.
• Active immunity involves humoral (B cells and antibodies/immunoglobulins) and cell-mediated (T cells) responses.
• Immunoglobulins recognize, bind to, and aid in the destruction of antigens (like bacteria & viruses).
• Passive immunity is the transmission of preformed immunoglobulins.
• Example: antibodies passed from mom to fetus OR transplant of plasma (which contain antibodies) from a donor to patient.

Pharmacodynamics of Antivirals (Oseltamivir) and Monitoring

• General pharmacodynamic principle: antivirals must block entry into the cell or be active inside host cells to be effective.
• Oseltamivir acts as a neuraminidase inhibitor, active against Influenza A & B.
• The inhibition of the neuraminidase viral enzyme prevents the release of the virus and halts the propagation of infection.
• Monitor renal function in older & debilitated patients.
• For older patients, evaluate for confusion, hallucination, and cognitive impairment.
• Initiate treatment within 48 hours of symptoms for prophylaxis AND treatment of Flu A & B.

Antiretroviral Therapy and Healthcare Provider Challenges

• Antiretroviral therapy (ART) is ONLY for HIV.
• HIV 1 is human, and HIV 2 is in animals.
• ART involves using a combination of 3 or more medications from 2 different classes to reduce the amount of HIV (viral load) in the blood.
• ART should be initiated within 14 days of diagnosis.
• ART regimen is determined by comorbid conditions, convenience, gender & pretreatment CD4 T cell count (nevirapine), and genotypic drug resistance testing.
• Consider human leukocyte antigen (HLA) B*5701 testing if considering abacavir.
• Evaluate patient adherence potential, potential adverse drug effects, potential drug interactions with other meds, and pregnancy potential.
• Challenges require multidisciplinary teams to optimize patient outcomes and engage/retain patients in their HIV care.
• Complex social problems include substance abuse, domestic violence, lack of child care, and unstable living conditions.
• Complex medication problems include lack of health insurance, opportunistic infections, mental illness, and chronic pain.
• Utilize state AIDS assistance programs or pharmaceutical co-pays.
• Resistance results from poor adherence, drug-food interactions, and abnormal pharmacokinetics, leading to detectable viral RNA levels in plasma.
• Discontinuation or interruption of ART due to concurrent illness, toxicity, surgery, or unavailable meds. leads to HIV viral load rebound, immune decompensation, and clinical progression.

Goals of Antiretroviral Therapy

• Achieve maximum suppression of plasma viral load for as long as possible.
• Delay medication resistance.
• Preserve CD4 T-cell numbers.
• Confer substantial clinical benefits, leading to reduction in morbidity and mortality.

Factors Increasing Antimicrobial Resistance

• Recent use of antibiotics.
• Overuse of broad-spectrum antibiotics.
• Age less than 2 years (due to daycare attendance) or greater than 65 years.
• Daycare center attendance.
• Exposure to young children.
• Multiple medical comorbidities.
• Immunosuppression.

Antibiotic Cross Sensitivity and Resistance

• Beta-Lactams & PCNs, Beta-Lactams & Cephalosporins: Both drug classes contain a beta-lactam ring vulnerable to beta Lactamase cell wall producing organisms.
• PCNs sensitivity (work against these).
• Natural PCNs are effective against Streptococcus, some Enterococcus strains, and some non-penicillinase producing Staphylococcus.
• Aminopenicillins exhibit greater activity against gram-negative bacteria due to an enhanced ability to penetrate the outer-membrane organisms.
• Aminopenicillins are used for gram-negative urinary and GI pathogens; examples: Escherichia coli, Proteus mirabilis, Salmonella, some Shigella species, and Enterococcus faecalis.
• Aminopenicillins are active against common gram-negative respiratory pathogens like Moraxella catarrhalis and H. influenzae type B.
• Beta-lactamase inhibitors, like clavulanate, sulbactam, and tazobactam, broaden the spectrum of activity when combined with beta-lactams.

Cephalosporins

• 1st generation: sensitive to gram-positive bacteria (S. aureus & s. epidermis).
• 2nd generation: sensitive to same as first generation, plus klebsiella and proteus.
• 3rd generation: sensitive to broader indications (treat gram + and -) but works better against gram negative bacteria.
• 4th generation: more broad and more resistant to beta-lactamase that inactivate 3rd generation, primarily works against gram positive bacteria (cover both but primarily gram positive bacteria).
• 5th generation: (Ceftaroline): similar to 3rd generation + active against MRSA.

Antibiotic Therapy for Strep Throat

• Appropriate primary and secondary antibiotic therapy for Strep throat (Group A Streptococcus) (ie if patient had allergy to primary antibiotic ).
• Primary beta Lactams (PCN V or Amoxicillin) or 1st generation cephalosporins (cephalexin) “cef drugs”.
• Secondary Patients with PCN allergy: Clindamycin or Azithromycin (** note strep dosing).

Antibiotic Side Effects and Management

• Monitor illness symptoms (are symptoms improving?), cultures before and after treatment, patient educations, completing entire dose.
• Maintain if working, change if not working or if culture results indicates different antibiotic.

"Watchful Waiting" and Antibiotics in Children

• Initial observation (48-72 hrs) without antibiotics for low risk patients (ONLY FOR AGES 2 AND UP/PATIENTS WITH NON SEVERE ILLNESS).
• Adequate pain mgmt is essential.
• Low Risk patient: Older than 2 years of age. Mild otalgia. Temperature less than 39 degrees Celsius/102.2 F.

"Safety Net Prescription"

• "WASP" "Wait and See Prescription".

Otitis Media Antibiotic Choices for Treatment Failure

• Treatment failure at 48-72 hours (ages 2 and up).
• If initially treated with amoxicillin or other first-line therapy and had failure: Augmentin or Ceftriaxone IM/IV for 3 days.
• PCN allergy: give Clindamycin + 3rd generation cephalosporin.

Tetracyclines

• Usage: treat bacterial infections
• Indications: Doxycycline: 1st line therapy for C. trachomatis (chlamydia) and Ureaplasma urealyticum. Tetracycline and minocycline treat P. acnes. Some H. pylori regimens include tetracycline.
• Contraindications: Do not prescribe to pregnant women (Category D), lactating women, or children aged less than 8 years. Use cautiously with patients who have renal or hepatic failure. Drug interactions antacids, zinc products, or magnesium-containing Laxatives (separate by 2h).

Urinary Tract Infections

• Urinary tract infections, treatments for all ages (See below).
• Review CDC and ACIP recommended vaccine guidelines: See the recommended vaccine schedule. Review CDC and ACIP recommended vaccine guidelines: See the recommended vaccine schedule.
• Children 0-18 years
• Adults
• Catch-up schedule
• Guidelines for vaccinating pregnant women.

Vaccine Schedule

• How to use schedule: determine recommended vaccine by age, then interval for catching up, then assess for additional need by medical condition, review vaccine type/frequency/interval/consideration, finally review contraindications/precautions.

CDC Recommendations

• CDC recommendations for: Clinical Use, dosages, contraindications, adverse drug reactions, timetable for administration in children and adults: MMR, Flu-Mist, Hep B, varicella

MMR

• Clinical Use: Prevent measles, mumps, rubella.
• Dose: 0.5mL SQ.
• Contraindications: Neomycin allergy, pregnancy, immunocompromised, febrile (ok to give to egg allergy or lactating patients).
• ADR: fever 7 to 12 days, drug interaction with IG, oral steroids, chemo.
• Time table: 2 doses first dose age 12-15 months, second dose 4-6 years or at least 4 weeks post 1st dose.
• ** one dose given to infant 6-12 months if traveling abroad but does not count as 1st dose **

Flumist

• Clinical use: prevent flu, live modified virus vaccine.
• Dose: intranasal spray, 0.2mL split between each nare.
• Contraindications: egg allergy, asthma, immunocompromised, pregnant.
• ADR: mild ADRs; nasal congestion, headache, sore throat, cough, muscle aches.
• Time table: annually to healthy pt's age 2-49 years ASAP in the fall.
• Children 2-8 years need 2 doses the first year.

Hep B

• Clinical use: prevent Hep B (stimulated anti hepatitis B surface antigen antibodies); inactivated virus vaccine.
• Dose: dependent on brand and age; usually IM but can given SQ.
• Contraindications: yeast allergy, moderate or severe illness, immunosuppression (give larger dose).
• ADR: local reaction, fever, malaise.
• Time table: all ages, 3 doses over 6 months 4 weeks between dose 1 and 2- 2 months between dose 2 and 3 4 months between dose 1 and 3.
• Newborn weighing less than 2,000 g receive 1st dose within 24 hours of birth.

Varicella

• Clinical use: prevent chickenpox; live virus vaccine.
• Dose: 0.5mL IM/SQ.
• Contraindications: neomycin allergy, febrile illness, immunocompromised, high dose oral steroids, pregnancy.
• ADR: fever, rash, injection site reaction.
• Time table: 2 doses first dose 12-15 months
• 2nd dose 4 to 6 years.
• Adolescents and adult with no history of vaccine give 2 doses at Least 4-8 weeks apart.

CAP and Therapy

• (Patients should be told to expect clinical improvement in 48-72 hours):
• Most common pathogen → Streptococcus pneumoniae
• Also most common pathogen in nursing homes, pregnant women, and peds (PRETTY MUCH ALL!)
• For patient with underlying lung disease: Haemophilus influenzae and Moraxella catarrhalis.
• Staph aureus usually co-pathogen with H. influenzae.
• Mycoplasma pneumoniae.
• Viral pneumonia.

Treatment for CAP

• Treatment is based on Infectious Disease Society of America and the American Thoracic Society Consensus Statement (2007):
• 4 classifications (only did first because last 2 are inpatient care)
• I: Previously healthy with no risk factors for drug resistant S. pneumoniae.
• Treatment: Macrolide (Level 1 evidence) Azithromycin or Clarithromycin, Erythromycin. Doxycycline if allergic.
• Treatment for a minimum of 5 days.
• II: Patients with risk factors (Adults with comorbidities of risk of drug resistant S. pneumoniae): Respiratory fluoroquinolones (moxifloxacin, gemifloxacin, or levofloxacin)
• Beta lactam PLUS a macrolide (amoxicillin, amoxicillin/clavulanate, or cefpodoxime, cefuroxime, parenteral ceftriaxone followed by oral cefpodoxime
• Doxycycline: may be used as an alternative to the macrolide
• OR for adults older than 60 with comorbidities: OP treatment option:
• Ceftriaxone (Rocephin) 1g daily via IM or IV or Levofloxacin 500 mg IV daily May switch to oral therapy once patient can tolerate oral medications
• III: Not admitted to the ICU
• IV: ICU patients
• Note: CURB 65- confusion, uremia, RR, BP, 65 or older
• Macrolides:
• Pregnancy Category B: erythromycin, azithromycin.
• Pregnancy Category C: Clarithromycin.
• If they have comorbidities or use of recent antibiotics: Beta lactam (PCNs) plus a macrolide

Pediatrics Treatment

• Under 5 years old: Bacterial PNA (S. pneumoniae).
• Treat: Amoxicillin 80-90 mg/kg/day
• Infant chlamydial PNA
• Azithromycin 20 mg/kg/day for 3 days OR erythromycin 50mg/kg/day for 14 days.
• The Ceftriaxone: 50mg/kg/day until able to take oral
• PCN allergy: clindamycin or a macrolide
• Older than 5 years: Mycoplasma PNA.
• Treat: Azithromycin 10 mg/kg on day 1, then 5 mg/kg on days 2-5
• Clarithromycin 15 mg/kg/day in 2 divided doses (max 1g per day).
• Erythromycin 40-50 mg/kg/day
• Understand contraindications for decongestants.
• Children under 4.
• Patients on concurrent MAOI therapy.
• Patients with severe HTN or CAD.
• Caffeine (maintain hydration).
• Refrain from smoking.
• Routine medication for newborns and medication for children with eye, ear, nose and throat disorders

Newborns

• Ophthalmia neonatorum (broad term)
• Gonococcal conjunctivitis: requires IM or IV ceftriaxone
• Prevention: erythromycin ointment within 1 hr of birth (only prevent gonococcal not chlamydial)
• Chlamydial conjunctivitis: requires treatment with systemic erythromycin

Children

• Bacterial conjunctivitis
• Children 3 months through 8 years are most likely to have staphylococcal,streptococcal, or Haemophilus conjunctivitis
• Treat: ophthalmic antibiotics (Ex: Bacitracin, “-mycin”, fluoroquinolones)
• Children younger than 6 years: most likely H. influenzae (73%)
• Treat: high dose amoxicillin-clavulanate
• Blepharitis (eyelash or eyelid inflammation)
• Treat: scrubbing eyelashes with gentle, no tears shampoo
• Erythromycin ointment
• Hordeolum (sty)
• Caused by S. aureus
• Treat: antibiotic eye drops or ointment
• Viral conjunctivitis
• Usually caused by adenovirus, herpes simplex or herpes zoster
• Treat: ophthalmic antibiotics
• Note: if herpes keratitis suspected refer to ophthalmologist

EAR

• Otitis Externa: “swimmers ear” treat with combo products with corticosteroids
• Acute: acid or alcohol drops (UNLESS PERFORATED ™)
• 4 drops for 7-10 days
• Prevention: 1-2 drops to dry the ear after swimming
• Chronic: treat with mineral oil daily, steroid cream
• Malignant OE: rare but lethal cause by pseudomonas aeruginosa; can cause
• osteomyelitis and meningitis
• Treat: parenteral antibiotics, an aminoglycoside and carbenicillin for 4-6 weeks,plus surgical debridement
• Otitis Media: caused by eustachian tube dysfunction
• Negative pressure causes reflux of bacteria into middle ear

Pathogens

• S. pneumoniae
• Nontypable H. influenzae
• M. catarrhalis
• Treat: wait and see for low risk patients over 2 years old
• 1st line: amoxicillin dose at 80-90 mg/kg/day OR combo drug amoxicillin-clavulanate 90 mg/kg/day
• PCN allergy: any of the "-cef" (cephalosporins)
• Treatment failure augmentin or ceftriaxone IM/IV
• **Initial observation only for acute otitis media ***

Nose

• Viral URI: most common rhinovirus
• Includes adenovirus, RSV, COVID, enteroviruses
• Typically lasts 7-9 days (if runny nose & cough on days 1-4, predictive of VIRAL origin)
• General URI
• Symptomatic care: fluids, antipyretics, nasal bulb suctioning in infants
• Decongestants ONLY in children age 4 and above
• Sinusitis: Systemic; pseudoephedrine, phenylephrine Topical" phenylephrine (neosynephrine) or oxymetazoline (Afrin)
• NO ABX
• First choice: amoxicillin (dose at 80-9- mg/kg/day in high-risk children for 10-14 days)
• 45 mg/kg/day in low risk children
• For PCN allergy: cefdinir, cefuroxime, or cefpodoxime
• If worse after 72 hours: switch to augmentin if amoxicillin was first choice, if on augmentin first, consider cefdinir, cefuroxime, cefpodoxime for children.

Throat

• Pharyngitis respiratory virus most common cause
• Most common treatment bacterial cause: Group A strep; confirmed by testing
• Treat: beta-lactams (PCN/Amoxicillin OR is gen cephalosporins like cephalexin)

Ophthalmic Beta blockers

• Treated by ophthalmologist
• Safety Monitor client for cardiac failure, hypotension, DO NOT abruptly stop, administer as prescribed
• Contraindications: Bradycardia/Heart Blocks, cardiogenic shock, CHF, ventricular dysfunction, poorly controlled DM because of prolonged hypoglycemia, Raynaud's disease***, PVD, Pregnancy Category C, with other BBs.

Influenza vaccine

• Influenzas: IM versus transnasal and understand administration in adults and children.
• Review contraindications
• Live attenuated Influenza (LAIV/Flumist)
• Administered intranasally (virus replicates in nasal mucosa)Live modified virus
• 2 strains Influenza A, 1 strain influenza B
• Contraindications: egg allergy, asthma, immunocompromised, pregnant
• ADR: mild ADRs: nasal congestion, sore throat, cough, muscle aches
• Dose: annually to healthy pts age 2-49 yrs (0.2mL split between each nare)
• ** Children 2-8 years need two doses the first year
• Inactivated Influenza
• Admin IM
• Killed virus
• 3 or 4 strain: 2 of type A; 1 or 2 of type B (Strains change annually based on predicated circulating strains)
• Contraindications: egg allergy, anaphylaxis to flu vaccine, Guillain-Barre syndrome within 6 weeks of flu vaccine, febrile ADR: local reaction, mild systemic effects
• Drug Interactions: immunosuppressants, theophylline, phenytoin, warfarin
• Dose: annual to age 6 months and up
• Younger than 9 years gets 2 doses first year
• High dose for 65+
• FluBlok or Flucelvax for pt with egg allergy

Attenuated live vaccines

• Live modified form of virus
• Contraindicated: pregnancy (avoid for 1 months post vaccination), immunocompromised.
• drug interaction antiviral drugs, sepate IG administration from live vaccine

URI Management Under 2 years

• Nasal bulb suctioning
• NO DECONGESTANTS****
• Avoid cough and cold medicines
• Reassure resolves in 7-10 days, little can be done to shorten course of disease
• No abx because its viral; symptomatic care only

Drugs action in the body

• CYP450 enzymes hepatic metabolism of drugs, used to break down majority of drugs
• Inhibitors of CYP450: drugs stay in system longer, can cause more ADRs or drug interactions
• Inducers: metabolize drug too fast, therefore little to no therapeutic effects happen,may need to increase dose
• Rifampin is a potent inducer of CYP3A4, thus decrease the effects of drugs that are coadministered with it
• With repeated administration, the half life of rifampin decreases.
• Stepwise approach to Asthma- know your Guidelines for Diagnosis and Management of Treatment of Asthma-specific to the first line therapies for each step, table 32–1 including intermittent asthma treatment plan
• The GINA Guidelines prefer an aggressive approach to gaining quick control (but can do either step up or step down approach)

1. Determine severity of asthma symptoms Use step therapy chart, and start at the recommended step.
2. Assess patient's response every 2-3 months Intermittent (less than or equal to 2 days a week): step one therapy Use short-acting beta agonists, as needed, for symptoms.

• Patients have symptoms when exposed to triggers (upper respiratory infections, allergens, chemical inhalants).
• Mild persistent asthma (>2 days/wk but not daily): Treat with low-dose inhaled corticosteroid medication daily Low-dose inhaled corticosteroids are the mainstay for patients of all ages

Moderate Asthma

• Manage using medium doses inhaled Coticosteroids
• With low dose, add Long term agonist and Leukotreine inhibitor
• Serve Persistant (multiple times a day).
• Medium/ High doses of interled long acting beat agent
• Requires consultation with a specialist as needed
• Use Aerochamber in infants and young children
• Side effect LTBA causes rapid Cardiac heart rate
• PEDS steps are similar but no the same. Use caution

Montelukast

• Montelukast works as a Lukotreine and receptor agonist
• Reduces muscle induction
• Used to help Persistent asthma symptoms
• Contradicted in women.
• HA is reported

Other drug groups

• Beta-Lactmas and Pcns should not be sued due to allergies
• Glycosylpes can lead to toxicity in the body

Antibiotics

• Azoles used for hepatotoxic
• Albendaole is given to parasitic infections. Take caution when using

Asthma

• Goal; Prevent chronic symptoms

• Low class is sued, if it does not work, then higher class is utilized.

• Risk is reduced by preventing emergency visits

• Drugs must be used for TB multiple times for organisms. The drug must be taken regularly. They must also continue for a long time

• First test the drug effectiveness, use multiple for great accuracy

• Two parts include initiation the first two minutes then conclusion phase when the four months

• When multiple, it is resistant so used at lead there new bugs!

• Pregnancy can be dangerous, do more testing on the patients

Otitis Media

• Try to use breast feeding as a prevention