Therapy

• *Gonococcal: discharge is yellow/green and profuse; severe dysuria; incubation of < 4 days
• *Nonspecific: gray or clear discharge mixed w/ mucous and slight; mild-moderate often intermittent dysuria; incubation 7-14 days

• *Mucopurulent or purulent discharge
• *Gram stain: >/= 5 WBC/oil field
• *Positive leukocyte esterase test or >/= 10 WBC/HPF on 1st void

• Neisseria gonorrhoeae
• Chlamydia trachomatis

Neisseria gonorrhoeae

• Chlamydia trachomatis
• Ureaplasma biovar 2
• Trichomonas vaginalis
• Herpes simplex
• Unknown (30%)

• *Dx based on clinical picture:
• -yellow endocervial exudate
• -endocervical bleeding induced by swab
• -increased # of PMN's on gram stain

• Men: 50%
• Women: 25%

• *Neonatal lung and eye infxn
• *PID

• *Azithroymcin 1g x 1 dose OR
• *Doxycycline 100mg po BID x 7 days

• *Azithroymcin 1g x 1 dose OR
• *Amox 500mg TID x 7 days

-Repeat testing 3 wks after completion of tx

• *Neonatal eye infections
• *PID
• *Bartholin's abscess
• *Disseminated gonococcal infxn

• *Culture all sites of sexual contact
• *Gram stain of urethral discharge (men)
• ->/= 5 WBC/oil field
• -intracellular G- diplococci

• *Ceftriaxone 125mg IM x 1 dose OR
• *Cefixime 400mg x 1 dose
• *PNC allergy: spectinomycin

-If chlamydia infectio is not ruled out by nucleic acid amplification test also treat for that (Azith or doxy)

• *Spread of gonorrhea to other parts of the body
• *Occurs in 1-3% of untx'ed pts (4:1 females:males)

• *Chills, polyarthralgias, fever, ans skin rash-->blood cultures often +
• *Septic arthritis, primary monoarticular-->blood cultures typically - but joint fluid often +

• *Hospitalization
• *Ceftriaxone 1g IV/IM q day until sx have improved for 24-48 h, then complete a 7 day course of PO
• *Tx chlamydia if not ruled out

• *N. gonorrhoeae
• *Chlamydia
• *M. hominis
• *Anaerobes: bacteroids and peptosteptococcus
• *Aerobes: G. vaginalsi, S. agalactiae, E. coli, H. influenzae

• *Infertility
• *Ectopic pregnancy
• *Chronic pain

• *Unterine/adnexal tenderness
• *Cervical motion tenderness

-Begin empiric tx if these criteria are present and no other cause can be ID'ed

*Standard regimen: Cefotetan 2g IV q 12 h OR cefoxitin 2g IV q 6 h + doxycycline 100mg PO or IV q 12 h x 14 days

*Prefered for abscesses: Clindamycin 900mg IV q 8 h + gentamicin 5mg/kg IV q 24 h

*Ceftriaxone 250mg IM x 1 OR Cefoxitin 2g IM x 1 + probenecide 1g PO x1

• *Plus doxycycline 100mg PO BID x 14 days
• *w/ or w/o metronidazole 500mg BID x 14 days

Tx presumptively for both Neisseria gonorrhoeae and Chlamydia trachomatis

• *Chancroid
• *Genital herpes

• *Syphilis
• *Lymphogranuloma venereum
• *Granuloma inginale

• *Painful
• *Caused by Haemophilus ducreyi
• *Rare in US
• *Increased risk of HIV
• *Incubation: 1-14 days (average 2-5)

• *Azithromycin 1g x 1 OR
• *Ceftriaxone 250mg IM x 1 OR
• *Cipro 500mg PO BID x 3 days OR
• *Erythromycin base 500mg PO TID x 7 days

• *Painless genital ulcer
• *Caused by calymmatobacterium granulomatis

*Caused by chlamydia serovas L1, L2, & L3

Females, minorities, older age, poverty, less education, cocaine use, # of partners

• *Most are due to HSV-2 (70-90%) {increase in GH due to HSV-1 in madison}
• *Typical case shows crop of painful vesicles that ulcerate and eventually curest over w/o scarring
• *Fever, malaise, myalgias, and tender lymphadenopathy common

• * 89% w/ HSV-2
• *precipitated by fever, sunlight, emotional stress, trauma, and menstration
• *asymptomatic viral shedding

*Tx will decrease: duration of viral shedding, time to crusting of lesions, duration of sxs, formation of new lesions after primary infection

• *Acyclovir: 200mg 5x/day x 7-10 days OR 400mg TID x 7-10 days
• *Famciclovir 250mg PO TID x 7-10 days
• *Valacyclovir 1g BID x 7-10 days

• *Acyclovir: 400mg TID x 5 days OR 800mg BID x 5 days OR 800mg TID x 2 days OR
• *Famciclovir 125mg BID x 5 days OR 1000mg BID x 1 day OR
• *Valacyclovir 500mg BID x 3 days OR 1000mg qd x 5 days

• *Indicated w/ >/= 6 episodes/yr
• *Tx for 1 year
• *Acyclovir 400mg BID OR
• *Famciclovir 250mg BID OR
• *Valacyclovir 500mg or 1000mg qd

• *Valacyclovir decreases overall viral transmission by 50%
• *Pearl: give to man only if man has HSV and partner doesn 't and wants to get pregnant

• *Screen w/ non-treponemal test (sensititve but non-specific)
• *Confirm dx w/ treponemal test (specific)

• *Primary: painless, solitary chancre w/o 10-90 days after infection and heals w/in 6 wks
• *Secondary: 2-8 weeks after chancre heals. Infectious skin leasions are maculo-papular (hands and soles); may have fever, malaise, pharyngitis, wt loss & nodes
• *Latent: asymptomatic
• -Early: infected <1 yr; infectious
• -Late: infected >1 yr; non-infectious
• *Tertiary: aortitis, vasulitis, gumm
• *Neurosyphilis: dementia, tabes dorsalis

• *Primary, secondary, or early latent:
• -Benzathine penicillin G 2.4 million units IM x 1
• -PCN allergy: doxycycline 100mg BID x 14 days
• *Late latent (or if unknown duration)
• -Benathine penicillin G 2.4 million units IM q week x 3
• *Neurosyphilis: IV PCN x 10-14 days

• *Chancroid: tender, purulent, undermined border
• *Syphilis: painless, indurated, not purulent
• *Herpes: multiple, painful, shallow, and not purulent

*16 & 18

• *Podofilox: 0.5% gel or soln BID x 3 days (repeat weekly up to 4 cycles)
• *Imiquimod: 5% crm TIW x 16 wks

• *Potent inducer of interferon
• *Crm weakens condoms/diaphrams
• *Works better in women (72%) than men (33%)

• *Cryotherapy q 1-2 wks
• *Podophyllin resin 10-25% weekly
• *Trichloroacetic acid 80-90% weekly
• *Surgical removal
• *Laser tx
• *Interferon alpha

*No tx recommendations

• *Approved in women >/= 30 yo
• -Cytology and HPV neg: rescreen in 3 yrs
• -Cytology neg and HPV pos: rescreen in 1 yr
• -Both positive: refer for colposcopy

• *Girls 11-12 (as early as 8 and late as 26)
• *3 dose series (0, 2, 6 months)

• *Metronidazole 500mg BID x 7 days OR
• *Metrogel 0.75% 5g intravaginally qd x 5 days OR
• *Clindamycin 2% crm 5g intravaginally qHS x 7 days

• *Metronidazole 2g PO x 1 dose OR
• *Tinidazole 2g PO x 1 dose OR
• *Metronidazole 500mg BID x 7 days

*Many options

• *Lindane 1% shampoo: apply for 4 minutes then wash off
• *Kids and pregnant women: permethrin 1% crm rinse to AA for 10 minutes then wash off

• -Wash linens and clothes used in past 2 days
• -Abstain from sex until partner tx'ed

• *Lindane (toxicity concerns)
• *Permethrin (requires complete coverage)
• *Ivermectin (?able safety, esp in kids)

• *Ceftriaxone 125mg IM x 1 AND
• *Metronidazole 2g x 1 AND
• *Azithromycin 1g PO x 1 or doxycycline 100mg BID x 7 days

• *E. coli
• *Klebsiella pneumoniae
• *Coagulase neg staph
• *Enterococcus
• *Grp B strep
• *Gardnerella vaginalis
• *Proteus mirabilis

• Pregnant women: isolation of bacteria from urine specimen
• Non-pregnant women: same bacterial strain isolated from 2 consecutive specimens in a quantity of >/= 1x10⁵ cfu/ml
• Men: single clean-catch urine w/ 1 bacterial spp in quantity of >/= 1x10⁵ cfu/ml
• Catheterized: single specimen w/ >/= 1 bacterial species in quantity of >/=1x10⁵ cfu/ml

• *Pregnant women
• *Pts undergoing prostate or urological surgeries
• *If persistent bacteriuria persits >48 h post-removal of catheter

-Tx to cover bacteria found on culture

• *Pre-menopausal adult females
• *Occasional infection
• *Upper and/or lower infection

• *Upper or lower tract infxns PLUS any of these 'risk factors':
• -Pregnancy
• -Male
• -Functional or anatomic abnormalities of the urinary tract
• -Immunosuppressed
• -Presence of catheter
• -Kids or elderly
• -Recurrent infxn

• *Frequency
• *Urgency
• *Dysuria
• *Suprapubic pain
• *Hematuria

• *E. coli (up to 90%)
• *Staph saprophyticus
• *Enterobacteriaceae
• *Enterocuccus

• *TMP/SMX x 3 days
• *FQ x 3 days

• *E. coli
• *Klebsiella pneumoniae
• *Citrobacter
• *Enterobacter
• *Serrotia
• *Proteus mirabilis
• *Providencia
• *Morganella morganili
• *Pseudomonas aeruginosa
• *Enterococcus

*Urine specimen for gram stain and quantitative culture

• *Levofloxacin
• *Ciprofloxacin
• *TMP/SMX
• *Nitrofurantion
• *Cefuroxime/cefpodoxime
• *Amox +/- clavulanate

-Tx for 7-14 days and obtain follow-up cultures in 10-14 days

• *Levofloxacin
• *Ciprofloxacin
• *Gentamicin/tobramycin (+/- ampicillin)
• *Amikacin (+/- ampicillin)
• *Cefuroxime/cefotaxime/ceftriaxone
• *Ampicillin + sulbactam
• *Pipercillin + tazobactam

• -After culture results, switch to PO
• -Obtain FU cultures in 10-14 days

• *Fever (>38 C)
• *Chills
• *N/V
• *S/sx of cystitis
• *Flank or abdominal pain
• *Costovertebral (CVA) tenderness

• *Same as cystitis --> E. coli most common
• *Perform urinalysis, urine, and blood cultures

• *Empiric tx: FQ OR TMP/SMX (if pathogen is known to be susceptible)
• *G+ organism: amoxicillin OR augmentin

*Tx PO for 7-14

• *Consider if pt is too ill or is unable to take PO
• *Tx for 10-14 days w/ 48-72 hours of IV tx

• *Empiric tx:
• -FQ OR
• -Ampicillin + aminoglycoside OR
• -3rd gephalosporin + aminoglycoside
• *G positive: amp/sulbactam +/- aminoglycoside

• *S/sx of UTI
• *No other IDable source of infxn
• *Single urine specimen w >/= 1 bacterial species in quantity of >/= 1x10³ cfu/ml
• *In pts with catheters or w/in 48 h of catheter removal

• *<30 days: single spp
• -E. coli (most common)
• -Ecterobacteriaceae spp
• -G+ cocci
• *>/=30 days: polymicrobial
• -organism above
• -P. mirabilis
• -Morganella morganii
• -Pseudomonas stuartii

• *Replace indwelling catheters that have been in place >2 wks (obtain culture from now catheter)
• *Tx for 7 or 10-14 days

• *Persistance of pre-tx organism
• *Often occurs <2 wks after completion of tx
• *Extensive urologic evaluation
• *Longer duration of tx
• *Defined as "complicated"

• *"New" infxn
• *Can be same or diff organism
• *Often occurs >2 wks after completion of tx
• *Occurs when sterile urine is documented btwn infxns
• *Majority of cases of recurrent UTIs
• *Common in young, sexually active women
• *Defined as "uncomplicated"

• *Perform urine culture to determine relapse or reinfection
• *Prevention w/ behavior modifications: contraception, post-coidal voiding, liberal fluid intake, cranberry juice, probiotics
• *Abx

• *Young women w/ >/= 2 symptomatic UTIs w/in 6 months -OR- >/= 3 symptomatic UTIs w/in 12 months
• *Tk pt's discomfort into concideration

• *TMP/SMX (80mg/400mg) TIW
• *Nitrofurantion 50-100mg qd
• *Cephalexin 250mg qd
• *Trimethoprim 100mg qd (not for post-coital)
• *Cipro 125mg qd

• *3 day course of:
• -TMP/SMX
• -FQ

*Instruct pt to contact provider if sx not resolved in 48 h

• *Tx not usually indicated
• *Tx only for high risk pts (low birth wt infants, neurtropenics, pts undergoing urologic manipulation)

• *1st line: fluconazole 200mg d x 14 days
• *Amphotericin B (via bladder irrigation or IV)
• *Flucytosine (PO)

• *Presentation: obvious sx of UTI, intense suprapubic pain, urinary obstruction, fever, malaise, arthralgia, myalgia
• *E. coli is most common pathogen
• *Get gram stain and culture and DO NOT examine and massage the prostate
• *A urologic emergency

• *Initial: PCN IV + AG
• *When stable: FQ po
• *Tx x 3-6 wks
• *F/U w/ culture in 7 days to ensure its clean
• *Consider NSAIDs to assist w/ pain and inflammation

• *E. coli most common, but increasing prevalence of G+ org. compared to acute prostatitis
• *Presentation: recurrent UTI sx's, perineal discomfort, fever
• *Dx made from analyzing prostatic secretions post prostatic massage

• *1st line: FQ (cipro or levo) -->assure G- etiology
• *TMP/SMX
• *Doxycycline

*Tx x 4-6 wks

*Cannot reach the bladder if CrCl <40 ml/min

The three membranes that cover the brain and spinal cord: dura mater, arachnoid mater, and pia mater

Inflammation of the subarachnoid space or spinal fluid

Meningitis belt: sub-Saharan Africa

• *Strep pneumoniae (most common)
• *H. influenzae
• *N. meningitidis
• *Listeria monocytogenes
• *Strep agalactiae
• *Aerobic G-: Klebsiella, E. coli, Pseudomonas, Salmonella
• *Staph aureaus (especially post-neurosurgery)

• *Viral: enteroviruses (most common), mumps, herpes, HIV, West Nile
• *Spirochetes: Treponema pallidum, Borrelia burgdorferi
• *Amebas

• *Severe HA
• *Nuchal rigidity
• *Altered mental status
• *Fever & chills
• *Photophobia
• *N/V
• *Sz
• *Kernig's and Brudzinski's signs
• *Cutaneous infections (esp in neonates)

• *WBC: <5-10
• -Elevated in all infections: Bacterial: >1000; Fungal and TB <500; Viral 50-1000
• *Neutrophils: predominant in bacterial infections and may be increased in viral infections
• *Glucose: 50-66% of serum
• -Decreased in all infections
• *Protein: <50 mg/dL
• -Increased in all infections

• *If there is a suspicion, get blood cultures and lumbar puncture STAT
• *Give dexamethasone and emperic abx tx
• *If CSF findings positive for bacterial meningitis target abx tx, if not continue ET (keep pt on dexamethasone either way)

• *Decreases subarachnoid space inflammatory response and overall decreases rate of mortality, severe hearing loss, and neurologic sequelae
• *Give w/ or just prior to 1st dose of abx
• *May reduce penetration of vancomycin into CSF

• *AG
• *Clindamycin
• *Amphotericin B
• *1st and 2nd gen cephlosporins (EXCEPT cefuroxime)

• *PCN G
• *Ampicillin
• *Cefotaxime
• *Ceftriaxone
• *Cefuroxime
• *Vanco
• *Meropenem
• *Linezolid
• *Cipro

• *Ampicillin + cefotaxime OR
• *Ampicillin + AG

• *Vanco + cefotaxime OR
• *Vanco + ceftriaxone

-If Listeria is suspected add ampicillin

• *Vanco + ampicillin + cefotaxime OR
• *Vanco + ampicillin + ceftriaxone

• *Vanco + ampicillin + cefepime OR
• *Vanco + ampicillin + meropenem

• *Vanco + cefepime OR
• *Vanco + ceftazidime OR
• *Vanco + meropenem

• *<50yo: Vanco + TMP/SMX + chloramphenicol
• *>50yo: Vanco + TMP/SMX

• *Cefotaxime OR
• *Ceftriaxone

-Tx x 7 days

• *Vanco + cefotaxime OR
• *Vanco + ceftriaxone

-Tx x 10-14 days

• *Ampicillin OR
• *PCN G

-Listeria and other G- tx for 21 days (or longer if immunocompromised)

• *Ceftazidime OR
• *Cefepime

• *Elevate head of bed 30 degrees
• *Hyperventilation
• *Hyperosmolar agents (ie: mannitol)
• *Steroids

• *Rifampin BID x 4 doses
• *Cipro x 1
• *Ceftriaxone IM x 1

-Recommended for household and daycare contacts and anyone directly exposed to pt's oral secretions

*Rifampin qd x 4

-Recommended for household contacts of unvaccinated kids <48 mo and possibly daycare contacts

*None but sickle cell pts may benifit form oral PCN tx

• *IV ampicillin or PCN G given intrapartum
• *If allergy, IV clindamycin or erythromycin given intrapartum

-Recommended for pregnant women if carrier + 1 risk factor (preterm labor, fever in labor, membrane rupture >18h ago, another child born w/ grp B strep disease)

*Vaccines!!!

• *Indolent onset of symptoms for >/= 4 wks
• *Physical exam may be normal

• *NSAIDs (ibuprofen most common)
• *abx
• *azathioprine
• *isoniazid
• *carbamaepine

-Tx by dc'ing causative agent + supportive tx

• *Nasal cavity
• *Pharynx
• *Larynx

• *Acute: sx <4 wks
• *Subacute: sx 4-12 wks
• *Chronic: sx that persist >12 wks
• *Recurrent: >/=4 episodes/yr w/ sx resolution btwn episodes

• *3 cardinal sxs: purulent nasal discharnge, nasal congestion and obstruction, & facial pain, pressure, or fullness or maxillary tooth discomfort
• *Other sx: sneezing, fever, fatigue, cough, ear pressure, HA, decreased sence of smell (hyposmia), and bad breath (halitosis)

• *Common causes: rhinovirus, influenza, parainfluenza
• *Self limiting sx resolution in 7-10 days
• *Abx NOT indicated

• *Consider bacterial when:
• -sx >/= 10 days
• -worsening sx w/in 10 days after initial improvement (possibly bacterial infection superimposed over viral)

• *Recommended:
• -Analgesics for pain/fever
• -Topical decongestants for drainage
• *Not benificial
• -Topical glucocorticoids for inflammation
• -Cough suppressants
• -1st gen antihistamines

• *Strep pneumoniea > H. influenzae > anaerobes = Streptococcus spp
• *Others: M. catarrhalis, Staph aureus

• *Presentation mild to mod & sx <7 days: OBSERVE
• *Presentation w/ sx >/=7 days:
• -OBSERVE if pts have mild pain and a temp <38.3 C/101 F
• -TX if pts have mod to severe sx's
• *Presentation mod to severe sx and temp >38.3 C/101 F: TX regardless of sx duration

• *1st line: amox, TMP/SMX, azithromycin, or erythromycin
• *If risk factors for drug-resistant pathogens: levo, cefuroxime, or augmentin

• -Tx x 10-14 days
• -Reassess pt in 7 days

• *If use of abx in previous 4-6 wks: FQ or high dose augmentin
• *If daycare child is in the household: high dose amox

• *Recommended:
• -Analgesics for pain/fever
• -Topical decongestants and mechanical irrigation for drainage
• -Topical glucocorticoids to decrease inflammation
• *No benefit:
• -Systemic decongestants or mucolytics for drainage
• -Cough suppressants
• -1st gen antihistamines for sneezing

• *Management: assess for modifying factors---> allergic rhinosinusitis, immunocompromised state, anatomic abnormality
• *Prevention: hand hygiene, smoking cessation, saline nasal irrigation

• *sore throat
• *tonsillar exudate
• *difficulty swallowing
• *fever and general malaise

• -More common in kids/adolescents
• -Seen seasonally in winter in spring

• *Primarily viral: rhinovirus, cornoavirus, adenovirus, HSV, parainfluenza, influenza
• *Bacterial: Group A strep > group C strep > group G strep

Streptococcus pyogenes

• *prevent acute rheumatic fever
• *prevent complications
• *improvement in sx
• *reduce transmission

• *Criteria: tonsillar exudates, tender anterior cervical adenopathy, fever, absence of cough
• *If 0-1 criteria: DO NOT test
• *If >/=2 criteria: TEST using rapid antigen detection test (RADT)

-Alternative tx strategy is to epirically trealy anyone w/ 3 or 4 criteria w/o testing

• *Rapid antigen detection test (RADT): rapid w/ excellent specificity but expensive and poor sensitivity w/ detection of "carriers" difficult
• -This is the first test preformed. If possitive tx. If negative do not treat unless its a child and then get a throat culture to assure dx.
• *Throat culture: gold standard by delay in results and determination of "carriers" is difficult

• *PCN VK po x 10 days (amoxicillin OK in kids due to bad taste of PCN)
• *Benzathine PCN G IM x 1
• *If PCN allergy: erythromycin or azithromycin x 10 days
• *If PCN allergy and macrolide resistant: clindamycin x 10 days

*The presence of fluid in the middle ear cavity

-Occurs in both acute otitis media and otitis media w/ effusion

An acute bacterial infection of the middle ear fluid:

• *Middle ear fluid that is not infected
• *No clinical s/sx of infection but frequently precedes AOM or follows its resolution

• *age (young)
• *daycare
• *breast feeding
• *tobacco smoke
• *pacifier use
• *FH

• *Otalgia (ear pain)
• *Hearing loss
• *Vertigo
• *Otorrhea (discharge) or swelling of the ear
• *Fever, irritability, HA, apathy, anorexia, vomiting, and diarrhea

• *Requires ALL of the following:
• -the presence of fluid in the middle ear (MEE)
• -h/o acute onset of sx
• -s/sx of middle ear inflammation

• *Strep pneumoniae
• *H. influenzea
• *M. catarrhalis

• *100% of M. catarrhalis and 50% of H. influenzae procude beta-lactamases
• *30% of Strep pneumo are resistant to PCN
• -Can be overcome by using increased doses of PCN

• *< 30 days from time of last abx use (esp w/ beta lactamase)
• *< 2 yo
• *Close contact w/ pts w/ AOM (ie: daycares)
• *Previous tx failure w. beta-lactam or macrolide antibiotic

• *Anyone with a "certain" diagnosis
• -although if >/= 2 yo and nonsevere illness (mild otalgia and fever <39 C), observaiton is an option
• *<6 mo even w/ "uncertain" diagnosis
• *6-24 mo w/ severe illness (mod to severe otalgia or fever >/= 39 C)

-Everyone else gets observation (defer x 48-72 hours)

• *1st line: amoxicillin 80-90mg/kg/day
• *PCN allergy w/ non-type 1 hypersensitivity: cefdinir, cefpodoxime, or cefuroxime
• *PCN allergy w/ type 1 hypersensitivity: azithromycin or clarithromycin

*Tx for 10 days unless >/=6 yo w/ mild to moderate disease, then tx x 5-7 days

• *Need coverage for H. influenzae or M catarrhalis (both produce beta-lactamases)
• -1st line: Amox/clav
• -PCN allergy (non-type 1): ceftriaxone
• -PCN allergy (type 1): clindamycin

*Tx for 10 days

*Ceftriaxone IM/IV x 1

-May be repeated q 48h x 3 total doses

• *Tx failure is no improvement after 48-72h
• *If inital tx was observation: tx w/ amox
• *Switch to amox/clav---> if failure, tx w/ ceftriaxone x 3 days---> if failure, clindamycin or surgery

*For recurrent AOM: >/= 3 episodes/6 months or >/=4 episodes/12 months

• *Viral (>90%): influenza A & B, parainfluenza, RSV, rhinovirus
• *Bacterial: Mycoplasma pneumoniae, Chlamydophila pneumoniae, & Bordetella pertussis

• *Persistent cough >5 days
• *Sputum production (often purulent)
• *Bronchospasms (decreased FEV₁)
• *Bronchial hyperreactivity

• -Fever is uncommon
• -Must rule out chronic bronchitis, pneumonia, postnasal drip, and asthma

• *Abx are DISCOURAGED (Canadian guidelines: if cough persists >10-14 days consider abx)
• *Disease is often self-limiting

• *Macrolide: azithromycin, clarithromycin, or erythromycin (GI AE's)
• *Abx is only of benefit only if begun <7 days but given if >7 days to limit spread of infection

*Mucus producing excessive cough on most days of the week for at least 3 consecutive months for 2 consecutive years or more

*A sudden clinical deterioration in a patient w/ chronic bronchitis

-Sputum is often colonized and thus sputum culture is not useful

• *Bacterial (30-50%)
• -Most common: H. influenzae, Step pneumoniae, M. catarrhalis
• -Advanced or severe disease: Pseudomonas aeruginosa & Enterobacteriaceae

*Exacerbations are often caused by acquisition of a new strain of bacteria

• Criteria:
• -Increased dyspnea
• -Increased sputum volume
• -Increased sputum purulence

• *Type 1 (severe): all 3 sx's
• *Type 2 (moderate): 2 sx's
• *Type 3 (mild): 1 sx ----> no tx indicated

• *Cardiac disease
• *>/=4 exacerbations/yr
• *Use of O₂
• *Lengthy duration of COPD
• *Malnutrition
• *FEV₁ <50% predicted

• *If type 3: no abx
• *If type 1 or 2: assess pt's Canadian risk factors for tx failure (FEV <50%, >/=4 exacerbations/yr, heart disease, use of home O₂, abx in last 3 months)
• -No risk factors: GROUP 1
• -1+ risk factors: GROUP 2
• -Multiple risk factors: GROUP 3

*Group 1 (no risk factors for tx failure): azithromycin, clarithromycin, 2nd or 3rd gen cephalosporin, amoxicillin, TMP/SMX, doxycycline

*Group 2 (1+ risk factor): beta lactam/beta lactam inhibitor (ie: amox/clav) or FQ

*Group 3 (multiple risk factors): Get gram stain and culture of sputum and tailor tx to pathogen

• *If no risk factors of tx failure use narrow spectrum abx:
• -Amox
• -TMP/SMX
• -Doxycycline

• *If risk factors for tx failure use broad spectrum abx:
• -Azithromycin
• -Clarithromycin
• -Amox/clav
• -FQ
• -2nd gen cephalosporins

• *SABA: 1st line bronchodilator
• *Antichoninergics: initiate after SABA is maxed out
• *Systemic steroids x 2 wks of pt requires hospitalization

-Mucolytics and methylxanthine bronchodilators are not recommended

• *Sx: cough, fever, sputum production, pleutritic chest pain
• *Inflitrate by chest XR

• *Determines severity of illness
• *One point given for each criteria to dermine 'score':
• -Confusion
• -Uremia (BUN >7 mmol/L or 20 mg/dL
• -RR (>30 bpm)
• -Low BP (SBP <90 or DBP <60)
• -Age >/=65

• *Score 0-1: tx outpatient due to low mortality
• *Score 2: consider supervised tx or hospitalization due to intermediate mortality
• *Score 3+: hospitalize pt and consider ICU due to high mortality

• *Another scale used to determine the severity of illness in CAP
• *Used to determine where to tx the pt
• -Class 1 & 2: outpatient
• -Class 3: outpatient, observation unit, or short hospitalization
• -Class 4 or 5: inpatient

• *Septic shock requiring vasopressor support OR
• *Respiratory failure requiring mechanical ventilation OR
• *Three of the following:
• -RR >/=30 bpm
• -PaO₂/FiO₂ ration </= 250
• -multilobar infiltrates
• -confusion/disorientation to person, place, or time
• -uremia (BUN >/=20 mg/dL)
• -leukopenia (WBC <4000 cells/mm³)
• -thrombocytopenia (platelet cout <100,000)
• -hypothermia (core temp <36 C)
• -hypotension requiring aggressive fluid resuscitation

• *Inpatient: sputum gram stain and culture & blood culture
• *Severe CAP: sputum gram stain and culture, blood culture, and urinary antigen tests for Legionella pneumophila and Strep pneumo

• *Strep pneumo
• *H. influenzea
• *Atypicals: M. pneumoniae, C. pneuoniae, Legionella

*ICU pts: pseudomonas and Staph aureus

• *Age <2 or >65
• *Beta lactam tx w/in last 2 months
• *Alcoholism
• *Comorbidities
• *Immunosuppessed
• *Exposure to a kid in daycare

• *Healthy w/ no use of abx in last 3 months: macrolide (preferred) -OR- doxycycline
• *Risk factor for drug resistant strep pneumo: respiratory FQ (moxi, gemi, or levo) -OR- beta-lactam (amox 1g TID, amox/clav 2g BID, ceftriaxone, defpodoxime, cefurxoime) + macrolide

• *Respiratory FQ (moxi, gemi, or levo) -OR-
• *Beta-lactam (cefotaxime, ceftriaxone, ampicillin) + macrolide

• *Beta-lactam (cefotaxime, ceftriaxone, or amp/sulbactam) + azithromycin -OR-
• *Beta-lactam (cefotaxime, ceftriaxone, or amp/sulbactam) + respiratory FQ (moxi, gemi, levo)

*If PCN allergy: respiratory FQ + aztreonam

• *Hemodynamically stable
• *Clinically improving
• *Able to ingest meds
• *Normally functioning GI tract

• *When clinically stable
• *Candidate for oral tx
• *No other active medical problems
• *Save environment for continued care

• *Minimum of 5 days!
• *Pt must be afebrile x 48-72h and has </=1 sign of clinical instability

-Longer duration may be needed for bacteremic S. aureus pneumonia, Pseudomonas, and other less common organisms

• *0-2 days of hospitalization: CAP
• *2-4 days of hospitalization: early onset HAP/VAP
• *5+ days of hospitalization: late-onset HAP/VAP/HCAP

*Pneumonia that occurs >/=48h after admission

-Classified as late onset if >/=5 days of admission

*Pneumonia that occurs >48-72h after endotracheal intubation

-Classified as late onset if >/=5 days of admission

• *Pneumonia associated w/ a risk factor for multi-drug resistant organisms:
• -Hospitalization for >/=2 days in teh preceding 90 days
• -Residence in a NH or LTCF
• -Home infusion tx
• -Chronic dialysis w/in last 30 days
• -Home wound care
• -Family member w/ MDR organism
• -IV abx in last 90 days
• -Immunosuppressed

• *New or progressing pulmonary infiltrate by CXR -PLUS-
• *Clinical evidence of infection (2 required)
• -Fever >38 C
• -Leukocytosis or leukopenia
• -Purulent secretions

*Requires respiratory tract culture: endotracheal aspirates or bronchoalveolar lavage

• *Limited spectrum antibiotics if early onset (2-4 days after admission)
• -Ceftriaxone OR
• -Levo, moxi, or cipro OR
• -Ampicillin/sulbactam OR
• -Ertapenem

• *Broad spectrum abx if late onset (5+ days after admission) to tx MDR pathogens
• -Cefepime or ceftazidime (covers pseudomonas)
• -imipenem or meropenem
• -pip/tazo + cipro or levo
• -AG + linezolid or vanco

• *Abx in preceding 90 days
• *Current hospitalization of 5+ days
• *High frequencey of abx resistance in community or specific unit
• *Any risk factors for HCAP
• *Immunosuppressed

---If a pt has any of these risk factors tx w/ BROAD SPECTRUM ABX---

• *Strep pneumo
• *H. influenzae
• *Staph aureus (methicillin-sensitive)
• *G-: E. coli, K. pneumoniae, Enterobacter, Proteus, Serratia marcescens

• *Early-onset pathogens
• *Pseudomonas aeruginosa
• *Klebsiella pneumoniae
• *Acintobacter
• *Legionella pneumophila
• *MRSA

• *Pseudomonas aeruginosa: use combo tx
• *Linezolid can be used as an alt to vanco
• *Acinetobacter: consider carbapenem, amp/sulbactam, or colistin
• *Avoid using a 3rd gen cephalosporin as monotx for ESBL producing Enterobacteriaceae--consider carbapenem or pip/tazo

*TB that is resistant to isoniazid AND rifampin

• *TB that is resistant to isoniazid AND rifampin -AND-
• *Resistant to any FQ -AND-
• *Risistant to at least one of the three injectable 2nd line anti-TB agents

• *Pulmonary TB is infectious (airborne droplet transmission)
• *Extrapulmonary TB and culture-negative pulmonary disease is non-infectious

• *Enlarging nodules obstruct bronchi and large airways cause lung colapse, obstructive emphysema, or bronchiectasis
• *Caseous necrosis causing destruction of lung parenchyma
• *Vasculature invasion leading to hemoptysis and reduced perfusion

• *Reactivation of latent TB
• *Fibrotic and calcified pulmonary lesion lead to progressively debilitating course led to the term 'consumption'

• *TB lymphadenitits
• *Genitourinary TB
• *Skeletal TB
• *TB meningitis
• *TB pericarditis
• *Disseminated TB

• *Rifampin (RIF)
• *Isoniazid (INH)
• *Ethambutol (ETB)
• *Pyrazinamide (PZA)

• *Most import and potent agent for TB
• *Blocks RNA synthesis
• *Great oral absorption and distribution (including meninges)
• *Excretion in bile and by kidneys
• *POTENT CYP INDUCER

• *Body fluid discoloration
• *GI upset
• *Hepatocellular injury
• *Rash

• *Should be included in all TB regimens unless the organism is resistant
• *Inhibits cell wall synthesis by inhibiting mycolic acid synthesis
• *Great oral absorption and good distribution (including meninges and caseous granulomas)
• *Hepatic metabolism
• *Renal elimination

• *Hepatotoxicity
• *Peripheral neuritis (administer w/ vit B6)

*DC if asymptomatic ALT >5x ULN or symptomatic >3x ULN

• *Pyridoxine (vit B6) 25-50mg PO daily
• *Helps w/ peripheral neuritis

• *Only active against mycobacteria
• *Inhibits cell wall synthesis
• *75% bioavailable w/ fair distribution (poor in CSF)

*Optic neuritis: loss of ability to see green, visual acuity testing monthly or w/ change in vision, slowly reversible

• *Prodrug converted to pyrazinoic acid in acidic environment of the phagocyte or caseous granuloma
• *Inhibits FA synthesis in Mycoplasm tuberculosis
• *Well absorbed w/ good distribution

• *Hyperuricemia
• *Polyarthralgias
• *Hepatotoxicity

• *Streptomycin
• *Fluoroquinolones: levo or moxi
• -Reserve for pts w/ MDR TB or who can't tollerate 1st line agents

• *Isolate pt!
• *QD regimen
• -RIF 600mg x 26 wks
• -INH 300mg x 26 wks
• -PZA 2000mg x 8 wks
• -ETB 15-25mg/kg x 8 wks
• *Direct observed tx: TIW
• -RIF 600mg qMWF x 26 wks
• -INH900mg qMWF x 26 wks
• -PZA 3000mg qMWF x 8 wks
• -ETB 25-30mg/kg qMWF x 8 wks

• *Use all:
• -Levo 750mg qd
• -PZA 2000-3000mg qd
• -ETB 25-30mg/kg qd
• -Streptomycin 10-15mg/kg IM/IV
• - +/- 2nd alternative agent

*Tx for 18-24 months!

• *4 to 6 drugs which the organims is susceptible to
• *tx for 18-24 months

• *Sputum cultures q2 weeks until 3 consecutive negatives, then monthly until tx complete
• -80% have neg cx at 2 mo
• -Positive cx at >3mo: tx failure, drug resistance, pt adherence

• *Hepatitis monitoring
• -baseline and q4 wk LFTs
• -pt to monitor for dark urine and loss of appetite

*Hyperuricemia: tx w/ ASA but DC PZA if gouty arthritis

*Optic neuritis: permanently DC ethambutol

*Autoimmune thrombocytopenia: permanently DC rifampin

• *Goal is to prevent active infxn (aka: "chemoprophylaxis")
• *Candidates for tx id'ed by PPD skin test

• *Isoniazid 300mg qd x 9 months -OR-
• *Isoniazide 300mg twice weekly (DOT) -OR-
• *Rifampin 300mg qd + pyrazinamide 2000mg qd x 2-4 months

• *53% male to male sexual contact
• *31% heterosexual contact
• *12% IV drug use

• *Standard tests: immunofluorescent assay or anzyme immunoabsorbant assay/ELISA
• *Confirmatory testing: Western blot (must use to confirm if ELISA test is postive)

-Sensitivity and specificity of >99.9%

• *HIV-1: type found most commonly in the US
• -2 major subgroups: M & O
• *HIV-2: type found primarily in West Africa
• -slower decline of CD4 count
• -standard viral load test inaccurate

• *T cell analysis which determines the extent of immune damage
• *Goal is >500 cells/mm3 (range: 500-1300)
• *Monitor at dx and q3-6 months

• *Measures the amount of HIV RNA in blood samples to determine the magnitude of HIV replication and rate of CD4 destruction
• *Used to evaluate the risk for disease progression and response to tx
• *Goal: undetectable (range= <50-1,000,000 copies/ml)
• *Monitor at dx, q3-6 months, and q2-8 wks after tx change
• *Avoid testing w/in 4 wks of immunizations or infections

• *HIV: infected w/ the human immunodeficiency virus
• *AIDS: having a CD4 count <200 or hx of an AIDS-defining illness

• *Candidiasis
• *Invasive cervical cancer
• *CMV
• *HIV-related encephalopathy
• *HSV
• *Histoplasmosis
• *Lymphoma
• *Pneumocystis carinni/jiroveci pneumonia
• *Recurrent pneumonia
• *Recurrent Salmonella septicemia
• *TB

• *NRTI: nucleoside/tide reverse transcriptase inhibitor
• *NNRTI: non-nucleoside reverse transcriptase inhibitor
• *PI: protease inhibitor
• *INSTI: integrase inhibitor
• *Entry inhibitor

Prevent entry of genetic material from the attached virus into the cell

• *enfuvirtide (FUZEON), T-20
• *maraviroc (SELZENTRY)

• *Entry inhibitor
• *FUZEON
• *Prevents fusion of viral and cellular membranes by binding to the first heptad-repeat in teh gp41 subunit of the viral envelope thereby preventing necessary conformational changes

• *Entry inhibitor
• *SELZENTRY
• *Selectively binds to the CCR5 receptor to prevent attachment of the gp120 and CCR5 to prevent entry of HIV-1 into the host cell

*Blocks reverse transcriptase to inhibit transcription

• *abacavir (ZIAGEN), ABV
• *didanosine (VIDEX), DDI
• *emtricitabine (EMTRIVA), FTC
• *lamivudine (EPIVIR), 3TC
• *stavudine (ZERIT), D4T
• *tenofovir (VIREAD), TDF
• *zidovudine (RETROVIR), AZT

• *TRIZIVIR: abacavir + lamivudine + zidovudine
• *COMBIVIR: lamivudine + zidovudine
• *EPIZICOM: abacavir + lamivudine
• *TRUVADA: emtricitabine + tenofovir

• *efavirenz (SUSTIVA), EFV
• *nevirapine (VIRAMUNE), NVP
• *delavirdine (RESCRIPTOR), DLV
• *etravirine (INTELENCE), TMC-125/ETR

*ATRIPLA: emtricitabine + tenofovir + efavirenz

*Inhibits integrase thereby preventing integration of HIV DNA into the host cell genome

• *Raltegravir (ISENTRESS), MK-0518
• -Only efficacious in HIV-1
• -No known drug interactions (not metabolized by CYP)

*Inhibits HIV protease resulting in the inhibition of viral maturation/proliferation

• *atazanavir (REYATAZ), ATV
• *amprenavir (AGENERASE), APV
• *darunavir (PREZISTA), DRV
• *fosamprenavir (LEXIVA), FPV
• *indinavir (CRIXIVAN), IDV
• *lopinavir/ritonavir (KALETRA), LPV/RTV
• *nelfinavir (VIRACEPT), NFV
• *ritonavir (NORVIR), RTV
• *saquinavir (FORTOVASE/INVIRASE), SQV
• *tipranavir (APTIVUS), TPV

• *Reduce HIV-related morbidity/mortality
• *Improve QOL
• *Restore and preserve immunologic fxn
• *Suppress viral load
• *Prevent HIV transmission

• *Hx of AIDS-defining illness
• *CD4 count <350
• *Pregnant
• *HIV-associated nephropathy
• *Co-infection w/ hep B when HBV tx is indicated

*Recommended, but not required, when CD4 count >350

• *Avoid neg effects on QOL
• *Avoid drug-related toxicity
• *Presserve future drug options
• *Delay development of drug resistance
• *Decrease total time on meds

• *Possibility of irreversible immune system depletion
• *Increased possibility of progression to AIDS
• *Possible increased riks of HIV transmission

• *2 NRTIs (tenofovir/emtricitabine) -PLUS-
• -NNRTI (efavirenz) -OR-
• -PI (boosted---> atazanavir + ritonavir or darunavir + ritonavir) -OR-
• -Integrase inhibitor (raltegravir)

*Fusion inhibitor, CCR5 antagonist not recommended for initial tx

• *Advantages:
• -Backbone of combo tx
• -Minimal drug interxns
• -PI and NNRTI preserved for future use

• *Disadvantages:
• -Lactic acidosis and hepatic steatosis reported
• -Triple NRTI regimens show inferior response compared w/ EFV- and IDV-based regimens

• *Advantages:
• -Long t1/2
• -PI and integrase options preserved for future use

• *Disadvantages:
• -Single mutations can cause resistance
• -Cross-resistance among the class of NNRTIs
• -Rash
• -Hepatotoxicity
• -Potential drug intrxns

• *Advantages:
• -High genetic barrier to resistance
• -PI resistance uncommon w/ failure (boosted PI)
• -NNRTI options preserved for future use

• *Disadvantages:
• -Metabolic complications (fat maldistribution, dyslipidemia, insulin resitance)
• -GI intolerance
• -Greater potential for drug interxns (esp w/ ritonavir)

• *Advantages:
• -Virologic response noninferior to Efavirenz
• -Fewer AE and lipid changes than Efavirenz
• -No food effect
• -Fewer drug interactions than PIs or NNRTIs

• *Disadvantages
• -Less long term experience
• -BID dosing
• -Lower genetic barrier to resistance than w/ boosted PI regimens
• -No data w/ NRTIs other than tenofovir/emtricitabine

*Tenofovir/emtricitabine (NRTIs) -PLUS-

• *Efavirenz (NNRTIs) -OR-
• *Atazanavir + Ritonavir or Darunavir + Ritonavir (PIs) -OR-
• *Raltegravir (II)

• *NNRTI-based: Efavirenz + didanosine + lamivudine
• *PI-based:
• -Atazanavir + abacavir --OR--
• -Zidovudine + lamivudine

• *Efavirenz is CI'ed in pregnancy
• *Atazanavir shouldn't be used if pt takes >20mg of omeprazole (or equivalent)
• *Lamivudine can be substituded for emtricitabine (or vice versa)
• *Nevirapine shouldn't be used in pts w/ hepatic impairment
• *Nevirapine shouldn't be used in women w/ pre-ARV CD4 >250 or men w/ CD4>400

*Efavirenz

-Especially in 1st trimester

*Lopinavir/ritonavir (BID) + zidovudine/lamivudine

*Atazanivir

*Didanosine + tenofovir

-Don't use as initial tx

• *3 class regimens
• *3 NRTIs + NNRTI

• *Stavudine + lamivudine
• *Indinavir + ritonavir
• *Ritonavir used as sole PI
• *Nevirapine

• *Monotx w/ NRTI
• *Dual NRTI tx
• *3 NRTI regiment (except w/ abacavir/lamivudine/zidovudine when other regimens are undesirable)

• *Didanosine + stavudine
• *Atazanavir + indinavir
• *2 NNRTI combos

*Stavudine + zidovudine

• *Saquinavir (unboosted)
• *Darunavir (unboosted)
• *Tipranavir (unboosted)

• *Lactic acidosis (highest w/ stavudine; stavudine> didanosine= zidovudine> tenofovir= abacavir= lamivudine= emtricitabine)
• *Hepatic steatosis (highest w/ stavudine; stavudine> didanosine= zidovudine>
• tenofovir= abacavir= lamivudine= emtricitabine)
• *Lipodystrophy (higher w/ stavudine)

• *Hypersensitivity rxn
• *Possibly increased risk of MI

• *GI intolerance
• *Pancreatitis
• *Peripheral neuropathy
• *Hepatotoxicity

• *Peripheral neuropathy
• *Pancreatitis

• *HA
• *GI intolerance
• *renal impairment

• *HA
• *GI intolerance
• *bone marrow suppression
• *anemia (Hg <7)
• *leukopenia (ANC <500)

-Monitor CBC q3 months or sooner

• *Rash
• *DD interactions

• *Hepatotoxicity (possibly life threatening)
• *Rash (including SJS)

• *Neuropsychiatric sx
• *Preg. cat. D (teratogenic in primates)
• *Rash

• *Hyperlipidemia
• *Insulin resistance & DM
• *Lipodystrophy
• *Elevated LFTs
• *Possible increased bleeding in hemophiliacs
• *Possible MI and CVAs

• *Hyperbilirubinemia
• *PR interval prolongation

• *GI intolerance
• *Rash

• *GI intolerance
• *Rash

• *Nephrolithiasis
• *GI intolerance
• *Hyperlipidemia
• *Hyperbilirubinemia

• *GI intolerance
• *PR interval prolongation

• *D
• *Possibly teratogenic and carcinogenic--by product has been in animal studies

• *GI intolerance: full dose rarely used (600mg BID) due to this
• -Combo w/ any other PI allows for lower doses
• *Hepatitis
• *Hyperlipidemia
• *Hyperglycemia
• *MANY DD INTERXNS!!!

*Must be refrigerated, but can remain at room temp for up to 30 days

• *GI intolerance
• *Rash
• *Hyperlipidemia
• *Liver toxicity
• *Cases of intracranial hemorrhage (increased risk w/ CNS lesions, head trauma, neurosurgery, coagulopathy, EtOH abuse, anticoag tx, vit E usage)

• *Inj site rxns
• *Hypersensitivity rxns
• *Increased risk of bacterial pneumonia

• *Abd pain
• *URI's
• *Cough
• *Hepatotoxicity
• *Musculoskeletal sxs
• *Rash
• *Orthostatic HoTN

• *N
• *HA
• *D
• *CPK elevation

• *MI and CVAs associated w/ PIs but not NNRTIs
• *Abacavir has possible increased risk of MI
• *Occurs months to yrs after starting tx
• *Risk factors: HTN, lipids, smoking, age, DM, FH
• *Avoid agents w/ higher risk

• *Rare but high mortality
• *Due to mitochondrial toxicity
• *Associated w/ NRTIs (esp d4t, ddl, ZDV)
• *Dx: lactate >2-5 mmol/dL plus sx's
• *Tx: DC ARV & supportive care

• *Severity is variable, usually asymptomatic
• *May resolve w/o tx interruption
• *May occur w/ all NNRTIs or PIs, some NRTIs and Maraviroc
• -Nevirapine: risk of severe hepatitis in 1st 18 wks of tx (monitor LFTs), increased risk w/ hep B/C, women, and hight CD4 count at initiation (women >250, men >400)
• -PI: esp RTV, RTV/SQV

• *Insulin resistance, hyperglycemia, and DM associated w/ all PIs, zidovudine, and stavudine
• *Screen FBS regularly

• *Peripheral fat wasting more associated w/ NRTIs (esp. stavudine)
• *Central fat accumulation more associated w/ PIs
• *Tx: switch to other agents (may slow or halt progression) or cosmetic txs

• *Elevatiosn in TC, LDL, and TGs
• *Associated w/ all PIs (except unboosted atazanavir)--> most w/ stavudine and afavirenz
• *Tx: consider ARV switch, lipid-lowering agents (caution w/ PI and certain statins)

• *Osteoporosis/osteopenia: associated w/ tenofovir and stavudine
• *Osteonecrosis: due to avascular necrosis
• -Associated w/ PIs, corticosteroid tx, EtOH abuse, hemoglobinopathies, hyperlipidemia, hypercoagulable states
• -Tx: surgical for severe disease, pain relief

• *Most common w/ NNRTIs (esp nevirapine)
• -most cases occur w/in 6 wks of tx
• -no benefit of prophylactic steroids or antihistamines
• *Also occurs w/ NRTIs (esp abacavir), PIs (esp amprenavir, fosamprenavir, darunavir, and tipranavir) and maraviroc

• *Associated w/ indinavir and tenofovir
• *Increased risks in pts w/ renal disease
• *Renal dosing w/ lamivudine, emtricitabine, and tenofovir

• *Associated w/ all PIs, zidovudine, and didanosine
• *Must rule out infectious causes
• *Tx: anti-diarrheal, anti-gas, and/or anti-emetic

• *Recommended prior to tx w/ abacavir to reduce the risk of hypersensitivity
• *If positive, don't initiate tx and deem pt "abacavir allergic"

• *HLA-B*5701 testing recommended
• *Sx's: fever, rash, fatigue, dyspnea, cough, abd pain, N/V/D
• *Usually occurs w/in 2nd wk of tx but can take up to 6 wks
• *Don't rechallange w/ drug----> can cause DEATH

• *Should be done prior to tx w/ maraviroc
• *CCR5 vs CXCR4 vs mixed tropism

• *Didanosine
• *Atazanavir
• *Delavirdine
• *Indinavir

• *nalfinavir---> needs high fat foods
• *efavirenz---> increased SEs w/ food
• *atazanavir---> 70% inc in AUC w/ food

• *Avoid simva and lova due to metabolism by CYP3A4
• *Pravastatin and fluvastatin have no drug interactions
• *<20mg atorva is acceptable

• *H2RA:
• -Avoid cimetidine due to CYP 3A4 inhibition ---> ranitidine or famotidine ok
• *PPIs:
• -Atazanavir should be avoided due to decreased absorption (can use H2RA if separated by >12h) but ok if equivalent dose of 20mg omeprazole qd
• *Antacids:
• -Separate from atazanavir and piranavir by 1-2h

• *PIs inhibit the 3A system and the ED drugs will therefore have higher concentrations
• *Use 1/2 the dose and extend teh interval to q48-72h
• -Sildenafil: <25mg/48h
• -Tadalafil: <10mg/72h
• -Vardenafil: <5mg/48h

• *Macrolides: avoid erythromycin; azithromycin the best choice
• *FQs: caution w/ DDI tabs
• *NO RIFAMPIN! (use only rifabutin at a reduced dose)

• *Dose adjustments needed for:
• -intraconazole
• -ketoconazole (w/ PIs)
• -posaconazole (causes increased levels of ritonavir and atazanavir; avoid w/ efavirenz)
• -voriconazole (w/ ritonavir and other PIs, efavirenz, and etravirine)

• *TCAs: amitriptlyine and desipramine interact w/ RTV and increase teh effects of both drugs
• *SSRIs: none
• *Trazodone: increased effect of traz w/ PIs thus use low doses

• *AVOID PHENYTOIN AND PHENOBARB
• *Gabapentin, levetiracetam, and topiramate have NO drug interxns
• *Lamotrigine: may need dose adj w/ lipinavir/ RTV

• *Prednisone: RTV increases AUC by 30% due to inhibition of 3A4
• *Probably minimal clinical significance but avoid if possible

• *Decreased effect of methadone w/ abacavir, atazanavir, efavirenz, lopinavir, nevirapine, and ritonavire
• *Decreases effects of didanosine

• *Efavirenz, nevirapine, or etravirine w/ PIs
• *Atazanavir + tenofovir
• *Didanosine + tenofovir
• *Didanosine + stavudine
• *Maraviroc + many PIs
• *Maraviroc + efavirenz or etravirine

*If nevirapine has been DC'ed for 2+ wks, restart w/ the usual dose escalation period

• *If pt also has hep B, may cause flair
• *Consider initiating adefovir or entecavir for HBV tx

• *Insufficient data to recommend planned tx interruptions
• *Risks: decline in CD4 count, disease progression, increase in HIV transmission, development of resistance
• *Benefits: reduction in drug toxicities, preservation of future tx options

*Paradoxical deterioration in clinical status after ARV tx initiation despite improved immune fxn due to inflammatory response against infectious antigen, which may or may not have been dx at initiation of ARV

-Typically occurs in pts w/ low inital CD4 (usually <50) and rapid decline in viral load; onset usually w/in 6 wks of ARV initiation but sometimes several months later

• *Pneumocystis jerovici
• *Fungus
• *Majority of pts exposed by the age of 2-4 yrs and infection is due to reactivation of latent infection or new exposure

• *Subacute onset of progressive exertional dyspnea, fever, nonproductive cough, & chest discomfort that worsens over a perior of days to wks
• *Hypoemia
• *CRX: diffuse bilateral symmetrical interstitial infiltrates

• *1st line:
• -TMP/SMX (15-20mg/kg/day based on TMP PO divided BID-QID)
• -Dapsone + TMP (use if pts intolerant of SMX)
• *2nd line:
• -Clindamycin and primaquine
• -Pentamidine
• -Atovaquone (better tolerated than TMP/SMX but administer w/ food due to poor bioavailability)

• *Tx x 21 days
• *Pt's clinical status can worsen over 1st 72h due to inflammatory responses
• *Steroids may improve survival in severe PJP

• *Primary: pts w/ CD4 </= 200
• *Secondary: all pts following initial episode of PJP
• *Tx may be DC'ed if CD4 >200 for >/=3 mo

*TMP/SMX: 1 ds qd or TIW (not as effective)

• *Caused by protozoan, Toxoplasma gondii
• *Host: cats
• *May spread through eating contaminated meats (esp lamb and pork)
• *Relapse is 100% once tx is stopped

• *Most common presentation of toxoplasmosis among AIDS pts
• *Risk increases as CD4 <100
• *Sxs: altered mental state, sz, weakness, cranial disturbances, sensory abnormalities, cerebral signs, meningism, movement disorders, neuropsychi manifestrations
• *Dx: CT scan w/ multiple bilat cerebral lesions, serologic testing to detect Ab's

• *Sulfadiazine + pyrimethamine
• *Administer w/ leucovorin bc drugs inhibit folic acid synthesis
• *Response usually seen in 7-10 days
• *Tx for 3-6 wks after sx's resolve
• *Tx-limiting SE observed in ~40% of pts

• *Clindamycin + pyrimethamine
• -administer w/ leucovorin
• *Pyrimethamine + [clarithromycin, azithromycin, atovaquone, or dapsone]
• *TMP/SMX

• *Primary prophylaxis: TMP/SMX (1 ds tab qd)
• -Tx if CD4<100 and + IgG ab titer
• -May DC tx if CD4 >200 x 3-6mo

• *Secondary: Pyrimethamine + sulfadiazine QID (w/ leucovorin)
• -May DC tx if pt has completed initial tx, pt is asymptomactic, and CD4 >200 x >6mo
• -Restart tx if CD4 <200

-Even w/ prophylaxis, 20-30% of pts will relapse

• *Caused by Cryptococcus neoformans from bird droppings
• *Common cuase of meningeal infection in HIV pts
• *More likely to occur if CD4 <200
• *FATAL if untx'ed
• *Mortality w/ tx= 25-30%
• *Sx's: nonspecific CNS-related, sz
• *Dx: examination of CSF: increased pressure, dec glucose, increased protein and WBCs (>/=20)
• *Not cleared from pts--->only suppressed

*Amphotericin B +/- flucytosine

• -Ampho causes rapid CSF sterilization
• -Continue until pt is afebrile and no N, V, HA then fluconazole may be initiated x 8-10 wks

*Fluconazone 400-800mg QD

• *Primary: not recommended
• *Secondary:
• -1st line: Fluconazole 200mg qd
• -2nd line: Amphotericin B IV qw-tiw
• -Tx until pt has completed initial tx, pt is asymptomatic for cryptococcus, and CD4 >100-200

• *Caused by a soil fungus, Histoplasma capsulatum
• *Pathogenesis is similar to TB
• *Tx: intraconazole

• *HIV pts are at 400-800x's greater risk
• *Tx for 6-9mo
• *Tx and prophylasis same as in 'healthy' individuals

• *Infection caused by M. avium or M. intracellulare
• *Occurs when CD4 count <100
• *Sx: fever, night sweats, wt loss, D, malaise, abd pain
• *Dx: blood cx

• *Clarithromycin/azithromycin + ethambutol + rifabutin/rifampin (+/- cipro/levo/amikacin)
• *Tx lifelong unless 12mo of tx and asymptomatic and CD4 >100 or >6 mo

• *Primary prophylasis: initiate when CD4 count <50-100
• -Azithromycin or clarithromycin or rivabutin
• -Can DC when CD4 >100 x 3-6mo

*Secondary prophylaxis until CD4 >100 x 3-6mo

• *Bloodborne pathogen
• *Likely to occur when CD4 <50
• *Tetinitis is the most common presentation but colitis also common

• *Primary when CD4 <50 and pt has CMV + ab's
• *Secondary prevention until CD4 >100 x 6mo

• *1st line: ganciclovir IV q12h x 14-21 days then IV qd or intraocular implant
• *2nd line:
• -Valganciclovir PO BID x 14-21 days then qd
• -Foscarnet
• -Cidofovir

• *Topical tx: nystatin or clotrimazole trouches
• *Systemic tx: fluconazole 100-200mg qd or itraconazole 200mg qd
• *Cont tx until sx's eliminated for several days

• *Pneumococcal: initial, 5 yrs later, and when >65 (if 1st immunization was w/ CD4 <200, revaccinate when >200)
• *Hep B: pts at risk esp if HCV
• *Hep A: pts at risk incl. co-infections w/ HBV HCV, IV drug use, MSM
• *Influenza

*Live vaccines CI'ed if CD4 <200

• *CD4 <200: PJP
• *CD4 <100: toxoplasmosis
• *CD4 <50: MAC, CMV, cryptococcus (if hx of)

• *Sporatic or infrequent disease
• *Mild to moderate
• *Likely to be Candida albicans
• *Non-immunecompromised women

• *3 day topical (same efficacy as 7 day), but if early in course 1 day tx can be recommended
• *Fluconazole PO

• *Recurrent (>/=4 episodes/yr)
• *Severe
• *Non-albicans candidiasis or
• *Uncontrolled DM, immunosuppression, pregnancy

• *Topical tx x 7-14 days
• *Fluconazole 150mg PO, repeat in 3 days
• *Immunocompromised: oral azoles or IV tx x 7-14 days
• *Pregnancy: topical azoles x 7 days

• *Fluconazole 150mg po q72h x 3 doses -OR-
• *Topical x 7-14 days

• *Tx x 6 mo
• -Fluconazole 1-2x/wk
• -Intraconazole
• -Clotrimazole
• -Boric acid
• _Gentian violet

• *Complete full course of tx
• *Use HS
• *If sx don't resolve in 24-48h see MD

• *Sx: intense vulvo-vaginal burning (as apposed to itching w/ albicans)
• *Tx:
• -Butoconazole
• Imidazoles x 7-14 days
• *Boric acid x 14 days
• *Topical gentian violet

***Fluconazole not recommended***

• *Swish and swallow oral susp QID
• *Contact PCP if increased irritation or no relief in 24-72h

• *Continue tx for 1 wk after lesion resolves
• *Infection is spread by human to human
• *If no improvement, see PCP bc oral tx may be needed

• *Systemic tx needed after spread to nail matrix
• *Terbinafine x 3 mo
• *Intraconazole x 3 mo
• *Griseofulvin x 12-24 mo

• *Broad spectrum antifungal w/ activity against dermatophytes
• *QD administration x 48 wks

• *Griseofulvin PO
• *Recurrent: terbinafine or intraconazole
• *Adjunct w/ topicals (selenium sulfide)

• *AEs: rash, HA, photosensitivity, NVD
• *DD intrnxs: decreased effects of warfarin and COCs, increased toxicity w/ EtOH

• *Candidiasis
• *Blasto
• *Histo
• *Cocci
• *Cutaneous dermatophytes

• *blasto
• *histo
• *aspergillosis
• *onychomycosis of the nails
• *dermatophytosis
• *chronic candidiasis
• *crypto
• *cocci