Therapeutics 523 Final Overview II
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Which SSTIs are considered uncomplicated?
- simple abscesses
- simple cellulitis
Which SSTIs are considered complicated?
- major abscesses
- diabetic foot infx
- pressure/decubitus ulcers
- necrotizing fasciitis
- severe cellulitis
- severe animal/human bites
Which SSTI-causing bacteria are frequently isolated in outpatients? In hospitalized patients?
- Outpatients - beta-hemolytic strep, staph aureus
- Hospitalized - Staph aureus, Pseudomonas, Enterococcus, E. coli
What are the most common pathogens in animal bites?
- Pasturella multocida
- Staph aureus
What are the most common pathogens in Human bites?
- Eikenella corrodens
- Oral anaerobes
Describe the presentation of impetigo
- small superficial fluid-filled vesicles
Treatment of impetigo
- Topical - mupirocin, retapamulin
- Oral - Penicillinase resistant pen (dicloxacillin) or 1st Gen Ceph (cephalexin)
- Suspected MRSA - TMP/SMX or doxy or minocycline
Describe the presentation of furuncles and carbuncles
- Furuncle is a boil - acute inflamm of SQ skin layers and hair follicles - occurs in skin areas containing hair follicles subject to friction and perspiration
- Carbuncle is more extensive - extends into SQ fat and develops into multiple abscesses
Groups at risk for CA-MRSA
- persons in correctional facilities
- players of contact sports
- military recruits
- native-american population
- males having sex iwth males
- IV drug users
- day care centers
- tattoo recipients
What are the transmission factors for CA-MRSA (5Cs)?
- crowded living conditions
- sharing contaminated personal items
- compromised skin
- frequent skin to skin contact
- lack of cleanliness
Groups/conditions that are risks for HA-MRSA
- LTC Facility residents
- pts with DM, HD
- prolonged hospitalization
- indwelling catheter
What bugs usually cause furuncles and carbuncles?How can it be prevented?
- Staph aureus (including CA-MRSA)
- These are often misdiagnosed as spider bites
- Prevention - good hygiene, keep lesions covered, avoid contact with drainage, launder shared clothing and equip
Treatment for furuncles and carbuncles
- lesions < 5 cm: only incision and drainage
- lesions > 5 cm: incision and drainage and abx tx
- Oral: TMP/SMX, TCs, Clindamycin (if D test neg), Rifampin, Linezolid, (no FQs)
- Parenteral: Vanco is DOC
Clinical presentation of cellulitis
- acute inflamm of epidermis and dermis that maylater spread into the superficial fascia
- s/s - tenderness/pain, erythema, hot, swollen
Clinical presentation of erysipelas
- type of superficial cellulitis with prominent lymphatic involvement
- predominantly in elderly
- lower extremeties and face involved
- Bright red indurated lesion, raised border sharply demarcated shiny erythematous plaque, bullae formation (severe)
Treatment of erysipelas
- 5-7 d course of abx
- Pen VK
- if CA-MRSA suspected, use TMP/SMX, doxy or minocycline, Pen G, if pen allergy can do IV clindamycin (if D test negative) or vanco
Treatment of cellulitis
- 7-10 day antibiotic course (14 d if severe)
- Penicillinase resistant pens: oral- dicloxacillin, parenteral- nafcillin
- 1st Gen Cephs: oral- cephalexin, parenteral- cefazolin
- If pen allergy - clindamycin or vanco
- If MRSA, DOC is vanco IV, can do linezolid IV or PO, daptomycin, etc
If a pt is seeking medical attention less than 8 hours after an animal or human bite, what is the treatment? What if it is 8-12 hours after?
- < 8 hours: general wound care or rabies and/or tetanus treatment
- 8-12 hours: treat for infx related complications
What is the treatment for animal bites? For human bites?
- Animal: copiously irrigate tear and puncture wounds, immobilize/elevate, surgical debridement if indicated; tetanus toxoid for those who need booster; consider rabies vaccine
- Human: irrigate, debride, immobilize; may need tetanus toxoid; consider viral disease of biter (HIV); prophylaxis of non-infected wound is recommended; if infx or clenched-fist injury treat with Abx
What is the duration of treatment and the abx therapy for bites?
- 5-10 days for treatment; 3-5 d for prophylaxis
- Oral DOC is amoxicillin/clavulanic acid
- Parenteral DOC is ampicillin/sulbactam
Describe the characteristics and s/s of necrotizing fasciitis
- characterized by: rapid spreading inflamm, necrosis of m., fascia, and skin, extensive inflamm of SQ tissue, progressively destroys fascia and fat
- s/s: hot, severe pain, swollen, shiny, tender, erythematous. Systemic sx are fever, chills, leukocytosis, shock, organ failure
- characteristics suggesting necrotizing infx: diffuse swelling followed by bullae, skin necrosis, gas bubbles in soft tissue
How is necrotizing fasciitis classified?
- Type I: polymicrobial - less serious - mixed aerobic/anaerobic - bacteriodes, peptostreptococcus, MSSA/MRSA
- Type II: truly flesh-eating - Group A Streptococcal (strep pyogenes) - without surgical interventions mortality is virtually 100%, with intervention it is 20-50%
Treatment of necrotizing fasciitis
- Surgical debridement of necrotic tissue
- Critical care support (fluids, ventilation)
- Empiric broad spectrum Abx - cover Streptococcus, Staphylococcus, Enterobacteriacae and anaerobes unless it is known to be Group A strep - Use a beta lactam with beta lactamase inhibitor (amp/sulbactam, pip/tazo) + cipro or gent + clindamycin + vanco
- If Group A Strep is identified, use Pen G + clindamycin
Categories of UTIs
- Acute uncomplicated cystitis/urethritis
- Acute uncomplicated pyelonephritis
- Asymptomatic bacteriuria
- Symptomatic abacteriuria (not a UTI)
In males are UTIs usually complicated or uncomplicated? In females?
- Complicated in males
- Uncomplicated in females
How is it determined that a UTI is complicated?
- there is structural of functional abnormality of the urinary tract
- not determined by age or organism
What constitutes a recurrent UTI?
>/= 3 episodes in a year
3 steps in treatment of UTIs
- 1. categorize the UTI (acute uncomplicated cystitis/urethritis or pyelonephritis, complicated, recurrent, bacteriuria, or prostatitis)
- 2. Determine patient-specific selection factors
- 3. Consider local susceptibility patterns
Which bacteria are usually the cause of uncomplicated UTIs? Complicated?
- E. coli
- P. aeruginosa
- Staph saprophyticus
- E. coli
- P. aeruginosa
- Enterobacter spp
When is single dose therapy used to treat UTIs?
Treatment for Acute uncomplicated cystitis
- 1. TMP/SMX x 3d
- 2. FQ x 3d
- 3. Nitrofurantoin x 7d
- 4. Beta-lactams x 3d (not as effective as bactrim or FQs)
- if pregnant
- 1. Amox-clav x 7d (not very good)
- 2. Ceph x 7d
- 3. TMP/SMX x 7d (avoid in 3rd trimester)
Treatment for Acute pyelonephritis - uncomplicated vs. complicated
- 1. FQ x 14d
- 2. Bactrim x 14d
- 3. Amox or amox/clav x 14d
- 1. FQ x 14d
- 2. Extended-spectrum pen + AG
Note: "cipro sucks" especially vs E.coli
Treatment for prostatitis
- 1st choice: FQ x 4-6 weeks
- 2nd choice: bactrim x 4-6 weeks
- Acute may initially require IV therapy
- Chronic prostatitis may require longer treatment periods or surgery
What is the only type of oral abx that covers Pseudomonas?
Which FQ shouldn't be used in a pt who has seizures?
When do we follow up with patients for acute uncomplicated cystitis, pyelonephritis, prostatitis, and recurrent UTIs?
- acute uncomplicated cystitis - no cultures needed unless pregnant, then culture at 2 weeks and monthly until delivery
- pyelonephritis - 2 weeks after abx course is complete
- prostatitis - f/u at 48-72 h because high failure/relapse rate. If still febrile, ultrasound. Add'ltesting for STDs in young men and partners
- recurrent UTI - consider bactrim 1 single strength qd, or 2 DS bactrim upon sx onset or 1 DS post coitus. In older women rule out obstruction - may consider nitrofurantoin qd, but renal fx and pulmonary fibrosis a concern. Topical estrogens reduce recurrence w/o risks assoc with HRT.
What are the most likely organisms to cause Meningitis?
- in 1 mo to 29 years, the Big 3 are N meningitidis, S pneumoniae, H influenzae
- in 30 - 70 years, N. meningitidis and S. pneumoniae are most likely
Is most meningitis acute or subacute?
- acute - this in an emergency - need abx asap
- note- subacute forms are usually not bacterial
s/s of meningitis
- fever, chills
- HA, backache, nuchal rigidity, mental status changes, photophobia
- N/V, anorexia, poor feeding habits (infants)
- Brudzinski's sign (hips and knees flex when neck is flexed)
- Kernig's sign (cannot straighten leg when hip is flexed to 90 degrees)
- bulging fontanel
Considerations regarding antibiotic penetration into the CNS when selecting therapy to treat meningitis
- low protein binding (more binding, harder to get into CNS)
- lipid soluble (more lipid soluble, easier to get into CNS)
- small molecular weight (higher weight, harder to get into CNS)
- unionized at physiologic pH (more polar, harder to get into CNS)
- absence or presence of meningeal inflammation (inflamm disrupts BBB making it easier to get through)
Empiric therapy for meningitis
- Neonates: ampicillin + 3rd gen ceph
- 3 mo - 50 yr: 3rd gen ceph +/- vanco
- > 50 years: 3rd gen ceph + ampicillin +/- vanco
Treatment for meningitis d/t Strep pneumoniae
- DOC is Pen G
- Alternatives - ceftriaxone, cefuroxime chloramphenicol, vanco (can add rifampin if using vanco as monotx)
- For Pen Resistant Strep pneumoniae - vanco + rifampin, FQ, linezolid
What are the risks and benefits of using adjunctive corticosteroid therapy in meningitis pts?
- significantly less hearing loss and other neurologic sequelae
- may decrease antibiotic penetration
When should corticosteroids be given when used in treatment of meningitis?
it is crucial that they be given before or at the same time as the antibiotics
Prophylaxis for meningitis
- S. pneumoniae - no chemoprophylaxis - vaccination
- H. influenzae - Rifampin (alt - FQs and ceftriaxone)
- N. meningitidis - Rifampin (alt - FQs and ceftriaxone); vaccination is best (esp in ages 2-5)
Therapy for meningitis d/t brain abscess
- metronidazole or chloramphenicol
What are the 3 most common bacteria that cause Acute Otitis Media?
- S pneumoniae
- H influenzae (most common)
- M catarrhalis
How do H. influenzae, M. catarrhalis, and S. pneumoniae resist antibiotics?
- H. influenzae and M. cat produce beta-lactamases
- S. pneumo changes its PBPs
How is Certain AOM diagnosed
- Must have 3/3 of the following:
- Acute onset (1-2 days)
- Presence of middle ear effusion (immobility, bulging)
- S/S of middle ear inflammation/infx (pain, irritability, tugging on ear, difficulty sleeping, fever, gray bulging nonmotile tympanic membrane)
Which risk factors for otitis media are associated with infection caused by resistant pathogens?
- young age (< 2 y.o.)
- previous episodes/abx exposure (within last month)
- day care attendance
What tympanic membrane findings indicate AOM?
- opaque, cloudy
- immobile or poorly mobile
Who do the current AOM treatment guidelines apply to?
- otherwise healthy children ages 2 mo - 12 years w/o underlying conditions
- Excludes recurrent AOM or OME
AOM treatment options for ages < 6 mo, 6mo-2yrs, and >/= 2 yrs for certain and uncertain diagnosis
- < 6 mo gets antibacterial therapy for certain and uncertain
- 6 mo to 2 yrs gets antibacterial therapy for certain diagnosis; for uncertain they get antibacterial therapy if severe illness, but if nonsevere they have the observation option
- >/= 2 years with certain diagnosis and severe illness gets antibacterial therapy, certain diagnosis and nonsevere illness gets observation option; with uncertain diagnosis, this group always gets observation option
Severe illness = "moderate/severe"otalgia OR fever >/= 39 degrees (102.2)
Initial treatment for AOM or for kids who fail initial observation after 48-72 hours
- If illness is not severe, first line tx is Amoxicillin 80-90 mg/kg/d divided BID.
- If illness is severe, first line tx is Amox/clav 90 mg/kg/d divided BID.
Which therapies are poor options for AOM and why?
- Bactrim d/t high rates of resistance to S. pneumoniae
- Erythromycin/sulfisoxazole d/t high rates of resistance to S. pneumoniae and frequent dosing
Duration of therapy for AOM
- children less than 2 years or those with severe illness - 7d
- children greater than or equal 2 years old with moderate illness - 5-7d
Which vaccines may help to prevent AOM?
- conjugate pneumococcal
What are the main bacteria that cause sinusitis?
- S. pneumoniae
- H. influenzae
- M. catarrhalis
How many days must a pt have s/s to diagnose sinusitis?
> 10 days
Treatment of sinusitis for mild symptoms lasting < 10 days
- nasal irrigation, humidified air
- cough suppressants and expectorants questionable
- antihistamines NOT useful for acute
- intranasal steroids questionable
Treatment of sinusitis when sx last >/= 10 days with no relief from supportive care.
Empiric abx for 10-14 days min
- For mild disease with no recent abx exposure:
- Any pt age, if not beta-lactam allergic, treat with amoxicillin or amox/clav, or cefdinir, cefpodoxime proxetil, or cefuroxime axetil
- If pt is beta-lactam allergic, can give TMP/SMX, macrolide/azalide, or doxycycline if over 18
- For mild disease with recent abx exposure or moderate disease:
- If less than 18 years, give high dose amox/clav or cefdinir, cefpodoxime or cefuroxime, or ceftriaxone
- If 18 or over, give a respiratory FQ, high dose amox/clav, ceftriaxone, or combo therapy (covering G(+) and G(-) orgs)
What is the most common mechanism of resistance to penicillins for S. pneumoniae, H. influenzae, and M. catarrhalis?
Under what conditions should antibiotics be initiated for a pt with sinusitis?
- moderate disease for 10+ days
- severe disease
- if s/s are worsening
Dosing of amox and amox/clav for sinusitis
- 500 mg - 1 g TID or
- 875mg - 2g BID
- or for kids, 90 mg/kg/d divided BID
Bacterial causes of pharyngitis
Group A beta-hemolytic strep (S. pyogenes) is most common
Clinical presentation of pharyngitis - the sx that are most suggestive of GAS pharyngitis
- fever > 38 degrees
- tonsillar exudates
- tonsillar edema
- cervical lymphadenopathy (tender)
- NO cough
What is the gold standard for diagnosis of pharyngitis?
What is the DOC for GAS pharyngitis? How is it dosed?
- if less than 12 years, give 250 mg PO BID-TID x 10d
- if older than 12 yrs, give 500 mg PO BID or 250 mg TID-QID x 10d
- could give 1 IM dose of penicillin benzathine (600,000 or 1.2 mil units)
What is the DOC for GAS pharyngitis in kids requiring a liquid formulation?
amoxicillin x 10 d
What is the most common cause of pharyngitis in 4-15 y.o. kids?
Three features that distinguish GAS from viral pharyngitis
- viral may be afebrile
- viral usually has no exudates
- GAS usually has no cough
What commonly causes infective endocarditis (IE)?
- bacteria (esp. G(+) aerobic orgs)
- atypical microorganisms
Which valves does IE commonly affect?
- the aortic valve and the mitral valve (left-sided)
- IV drug users have infx on the tricuspid valve more often (right-sided)
Risk factors for IE - infective endocarditis
- Hx of IE
- Heart valve abnormalities (e.g. prosthetic valves, valvular dysfxn, mitral valve prolapse)
- IV drug abuse
- prolonged hospital stay
Pathophys of infective endocarditis
- Endocardium is damaged leading to platelet aggregation and activation of clotting cascade - fibrins deposited on endocardial surface
- Bacteria colonize these surfaces
- Inflamm/immune response is activated, but fails to eliminate the bacteria - bacteria, platelets, fibrins, debris entangle and vegetations grow
- Vegetation can protect bacteria, cause more valve damage, break off and become septic emboli, or facilitate antibody formation that may lead to more inflamm and tissue damage
Complications of IE
- permanent heart valve damage
- heart failure
- microembolic events
Most common pathogens that cause IE
- gram-positive cocci (esp. strep and staph)(also enterococcus)
- gram negative orgs - HACEK group (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella corrodens, Kingella kingae)
- For IV drug users, add MRSA, and Pseudomonas
- Fungi and atypical orgs are uncommon - would be more in immunocompromised pt
What is the mainstay of therapy for IE? What is the best management for high risk patients?
- drug therapy is the mainstay
- surgery is best for high risk pts
Treatment for infective endocarditis
- supportive care
- IV antibiotics (long duration)(use BC agents)
- Consider short-term use of rifampin and/or gent for synergy
- Antimicrobial regimen selection depends on:
- if the pt has their own natural (native) valves or prosthetics
- pt-specific factors (e.g. concerns with IV drug users = co-infections and different causative organisms and polymicrobial infx)
- etiologic organisms and their drug susceptibilities and unique properties
Empiric therapy for infective endocarditis
Vanco + Gent +/- Rifampin
Antimicrobial therapy for patients with native valve IE
- if Viridans or S. bovis, therapy is 2-4 weeks. Use Pen G, or Ceftriaxone. Can add gent SDD for synergy. Use vanco only if pt can't tolerate pens or cephs.
- if Staphylococci (aureus or epidermidis), therapy is 6 weeks. Use Nafcillin or Oxacillin or cefazolin. Can add Gent for synergy.
- for HACEK organisms, therapy is 4 weeks. Use ceftriaxone or amp/sulbactam or cipro
What drug is FDA indicated for treatment of S.aureus bacteremia, including those with right-sided infective endocarditis caused by MRSA/MRSE?
Is antimicrobial treatment of IE longer in pts with native valves or those with prosthetic valves?
Care during and after the completion of antimicrobial treatments in IE
- Get TTE
- drug rehab referral for IVDUs
- dental eval
- remove IV catheter promptly
- short-term - get 3 blood cultures, PE for evidence of CHF, eval for toxicity from abx therapy
- long-term - get 3 blood cultures, eval valvular and ventricular fxn using echocardiography, oral hygiene and freq dentist visits very important
Name conditions with the highest risk of adverse outcomes from IE for which prophylaxis with dental procedures is reasonable.
- prosthetic cardiac valve or prosthetic material used to repair cardiac valve
- previous IE
- congenital heart disease (or if repaired, for the 6 months after the procedure)
- cardiac transplant recipients with cardiac valvulopathy
Dental procedures for which IE prophylaxis is reasonable for pts with cardiac condition at risk for IE
any that involve manipulation of gingival tissue or the periapical region of teeth or perforation of oral mucosa
What meds are used for IE prophylaxis regimens before dental procedures? When should the meds be taken?
Amoxicillin is DOC - take 30-60 min before procedure
A child's acid output remains low until they are how old?
Gastric emptying and intestinal transit time are prolonged in children until what age?
Are IM and SQ absorptions high or low in neonates?
What happens to extracellular body water content and body fat as a baby ages?
extracellular water content decreases and body fat increases
Which antibiotics have larger volumes of distribution in children than in adults? Why is this important?
- hydrophilic abx such as AGs and vanco (lipid soluble have lower Vd in children)
- Important because they require larger doses than adults
Is plasma protein binding increased or decreased in neonates?
Name 2 antibiotics that displace bilirubin from albumin. What is the significance of this in neonates?
- risk of kernicterus
Is membrane permeability higher or lower in neonates?
higher (so CNS and RBC permeability may be enhanced)
Limited ability of infants to perform glucuronidation may lead to what condition?
gray baby syndrome with chloramphenicol
When do GFR, tubular secretion and reabsorption reach mature levels in kids?
by 3 years
Do AGs and Vanco have a larger or smaller Vd in peds than in adults? Is their clearance increased or decreased?
Antimicrobials to avoid in neonates
In neonates and young infants the Vd of AGs is _____ and the renal clearance is _______ than in older children.
What is CCR5 and which drug inhibits it?
- CCR5 is the most common receptor site on the CD4 cell for the binding of HIV
- Maraviroc is a CCR5 inhibitor
What are the SEs of maraviroc?
myopathies and rhabdomyolysis
What medication is a fusion inhibitor? What are its SEs?
Name the NRTIs
Name the NNRTIs
What drug is an integrase inhibitor? What are its SEs?
Name the protease inhibitors
What are class effects of NRTIs?
- lactic acidosis
- peripheral neuropathy
Class effects of NNRTIs
- complete cross-resistance
What are the class effects of protease inhibitors?
- metabolic syndrome (lipodystropy, dyslipidemia, hyperglycemia)
- elevated transaminases
What are the fixed dose combos for HIV meds and what drugs are in each?
- Epzicom (abacavir + lamivudine) (2 NRTIs)
- Trizivir (abacavir + lamivudine + zidovudine) (3NRTIs)
- Atripla (efavirenz + emtricitabine + tenofovir) (NNRTI, 2 NRTIs)
- Truvada (emtricitabine + tenofovir) (2 NRTIs)
- Combivir (lamivudine + zidovudine) (2 NRTIs)
Which NRTI has a SE of life-threatening hypersensitivity?
Which NRTI has a SE of pancreatitis?
Which NRTI can exacerbate HepB infx when it is D/C'd?
Which NRTI has pancreatitis and peripheral neuropathy as SEs?
Which NRTI is nephrotoxic and hepatotoxic?
Which NRTI causes bone marrow suppression?
Why does efavirenz need to be taken on an empty stomach?
Fatty meals increase its absorption, so CNS effects would increase
Nevirapine causes liver toxicity. Don't use in pts with CD4 counts of ______?
- females with CD4 > 250
- males with CD4 > 400
Which PIs are sulfonamides?
What HIV med is used as a booster for PI therapy?
Which PI causes nephrolithiasis?
What is the preferred PI for pregnancy?
Which PI can cause intracranial hemorrhage?
Which PI is used for salvage therapy and can cause QT prolongation?
If an HIV regimen needs to be changed d/t suspected drug failure, how is it done?
change all agents involved in the regimen if possible
What is HAART?
- treatment with at least 3 anti-retroviral meds
- usually 2 NRTIs plus a NNRTI or PI or another NRTI
What is the preferred NNRTI based regimen for treatment naive patients?
What is the preferred PI based regimen for treatment naive patients?
- atazanavir with ritonavir
- tenofovir with emtricitabine (or lamivudine)
- darunavir with ritonavir
- tenofovir with emtricitabine (or lamivudine)
What is the preferred INSTI based regimen for treatment naive patients?
- tenofovir with emtricitabine (or lamivudine)
What is the preferred antiretroviral regimen for treatment naive pregnant women?
- lopinavir with ritonavir
- zidovudine with lamivudine (or emtricitabine)
Things to remember for antiretroviral treatment regimens for treatment naive patients
- Abacavir and zidovudine are never used together
- Didanosine is not listed in the preferred or alternative regimens on the chart
- Nevirapine must be with zidovudine
What are the classes used in initiating antiretroviral treatment in a treatment naive patient?
- a 2 NRTI backbone
- plus either an NNRTI or a PI (boosted)
What is IRIS?
- Immune Reconstitution Inflammatory Syndrome
- occurs when new antiretroviral regimen is started
- may unmask undetected opportunistic infx
- Pathogens of concern are Pneumocystis, MAC, CMV
9 common pathogens that cause opportunistic infx in HIV patients and the treatment for each
- 1. Pneumocystis jiroveci - bactrim x 21 d
- 2. Toxoplasma gondii - pyrimethamine (must use leukovorin with it) + sulfadiazine
- 3. Cryptococcus neoformans - Ampho B + flucytosine, then fluconazole
- 4. Mycobacterium tuberculosis
- 5. MAC - clarithromycin + ethambutol +/- rifabutin
- 6. Cytomegalovirus - Ganciclovir or valganciclovir or foscarnet
- 7. Candida - fluconazole or nystatin or clotrimazole
- 8. Cryptosporidiosis - immune reconstitution
- 9. Microsporidiosis - symptomatics
What is the breakpoint value for Pneumocystis jiroveci, Toxoplasma gondii, and MAC?
- P. jiroveci is < 200
- T. gondii is < 100
- MAC is < 50
What is the treatment for Pneumocystis jiroveci, including adjuvant tx?
- Bactrim x 21 d
- Pentamidine IV
- Clindamycin + primaquine
- Adjuvant - glucocorticoids (methylpred)
What is the treatment for Toxoplasma gondii, including adjuvant tx?
- Pyrimethamine + sulfadiazine
- Pyrimethamine + clindamycin
- Adjuvant - avoid cat poop
What is the treatment for MAC, including adjuvant tx?
- clarithromycin + ethambutol + rifabutin
- adjuvant - watch absorption of ARV
What are the 1st line agents for TB?
- For active TB infx, use all 4 of these together
What are second line agents for TB infx?
- PAS (p-Aminosalicylic acid)
Treatment of Active TB
- 2 months with INH/RIF/EMB/PZA
- then 4 mo with INH/RIF
- then 3 more mo with INH/RIF if cavitation
What are 5 classes of antifungals? Give examples of each.
- azoles (fluconazole, itraconazole, posaconazole, voriconazole)
- polyenes (Amphotericin B)
- echinocandins (Anidulafungin, Caspofungin, Micafungin)
- antimetabolites (flucytosine)
- allylamines (terbinafine)
Which antifungal class has nephrotoxicity as its primary toxicity?
polyenes (Ampho B)
Which azole has particularly poor activity vs. non-albican species?
Which azole antifungal is renally eliminated? What is the main toxicity of the azoles?
Which azole antifungal may need therapeutic drug monitoring and why?
voriconazole because it exhibits non-linear elimination
Which azole antifungal has saturable oral absorption? What does this mean in terms of dosing this agent?
- the absorption doesn't increase with doses larger than 200 mg, so even though its half life is 25-30 hours, it must be administered tid to qid
What is a normal dose for each of the following? Ampho B, Fluconazole, Liposomal Ampho B, Micafungin, Flucytosine, Voriconazole, Posiconazole
- Ampho B: 1mg/kg IV QD
- Liposomal Ampho B: 5 mg/kg IV qd
- Fluconazole: 400 mg IV qd
- Micafungin: 150 mg IV qd
- Flucytosine: 100 mg/kg PO qd
- Voriconazole: 300 mg PO bid
- Posaconazole: 200 mg PO tid
What body parts/systems are commonly colonized by Candida spp?
- Female genitourinary tract
Do candida infx usually arise from endogenous or exogenous sources?
- compromise of host defenses/immune fxn can lead to infx
Risk factors for Candida infx
- exposure to broad-spectrum Abx
- placement of a central venous catheter
- use of parenteral nutrition
- GI or cardiac surgery
- prolonged hospitalization
- ICU stay
- thermal injury
- premature birth
- use of corticosteroids
- HIV infx
Common Candida spp that cause human infx. Which of these are most worrisome and why?
- C. albicans
- C. glabrata
- C. tropicalis
- C. parapsilosis
- C. krusei
krusei and glabrata are the most concerning because they have lots of resistance - esp to azoles
Which antifungals are C. glabrata and krusei resistant to? Which are they susceptible to ?
- resistant to azoles
- susceptible to Ampho B and echinocandins
What is the best treatment for candidemia caused by Candida?
- Echinocandins are preferred
- Can use fluconazole if pt is hemodynamically stable, non-neutropenic, and C. glabrata or krusei is not suspected
What is the treatment for invasive candidiasis?
- if pt is hemodynamically unstable or neutropenic: use liposomal Ampho B, and echinocandin, or voriconazole
- if pt is hemodynamically stable and non-neutropenic, but C. glabrata or krusei is suspected: use echinocandin
- if pt is hemodynamically stable and non-neutropenic and C. glabrata and krusei are not suspected: use fluconazole or echinocandin
What is the duration of therapy for candida infection?
- at least 14 days
- if disseminated, it is months
Where is Aspergillus spp commonly found?
- construction sites
Risk factors for acquiring Aspergillus
- prolonged neutropenia (< 100)
- advanced HIV
- inherited immunodeficiency
- transplantation pts
Is Aspergillus infection usually from an endogenous or exogenous source?
What type of drugs can facilitate the virulence of Aspergillus? How?
- decrease the oxidative killing by macrophages
- may promote cell growth
What radiographical findings indicate a diagnosis of aspergillosis?
- Not chest x-ray
- CT scan - halo sign and air crescent
What is the treatment for Aspergillosis?
- Primary - Voriconazole is DOC, could also use ampho B, echinocandins (don't kill hyphae, so the Asperg. could keep growing later on), or other azoles
- Salvage therapy - if lack of response or tolerance to another agt
- Duration of treatment is at least 6-12 weeks
- Neutropenic patients should receive colony stimulating factors
What is the infecting organism for Bacterial Vaginosis and what is the treatment?
- it is polymicrobial - mostly anaerobic bacteria like G. vaginalis, Mycoplasma, Ureaplasma
- treatment is Metronidazole or Clindamycin
Infecting organism and treatment for Chlamydia
- Chlamydia trachomatis
- Azithromycin 1 gram x one single dose
- Doxycycline 100 mg BID x 1 week
Infecting organism and treatment for Genital Herpes
- HSV-1 or HSV-2
- no cure
- suppressive therapy - acyclovir, famciclovir, valacyclovir
Infecting organism and treatment for Genital Warts
- 90% of the cases are cleared by the immune system within 2 yrs
- no cure - treat outbreaks - Podofilox, Imiquimod
- Prevention - Gardasil Vaccine - the 6 & 11 are the ones that cause warts (16 & 18 cause cervical cancer)
Infecting agent and treatment for Gonorrhea
- Neisseria gonorrhoeae
- Treatment is curative - Ceftriaxone 125 mg IM single dose, or Cefixime 400 mg orally in a single dose
Infecting organism and treatment for pubic lice
- Pediculosis Pubis (an ectoparasite)
- Pediculocides - permethrin or pyrethrin
- Alt - malathion or ivermectin
Infecting organism and treatment for scabies
- Sarcoptes scabiei
- Permethrin or ivermectin
- alt - lindane
Infecting org and treatment for syphilis
- Treponema pallidum
- Penicillin - Single IM dose for infx of less than one year
Infecting org and treatment for Trichimoniasis
- Trichomonas vaginalis
- Metronidazole 2 grams PO single dose
- or Tinidazole 2 g PO single dose
- or metronidazole 500 mg PO BID x 7d
What is the most appropriate therapy for PID?
Cefotetan 2 g IV q12h
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