Infectious Disease

1
Infectious Disease
Infectious Disease

2
Emerging Pathogens

• Anthrax
• Vancomycin-resistant enterococcus (VRE)
• Penicillin-resistant Strep pneumoniae
• Methicillin-resistant Staph aureus (MRSA)
• West Nile virus

3
Anthrax

• Inhalation Anthrax is not pneumonia
• Hemorrhagic mediastinitis, widened mediastinum on
  CXR
• Inhaled spores deposit in lungs Macrophages take
  to mediastinal lymph nodes. Spores germinate
  resulting in overwhelming sepsis and toxin
  production

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Inhalation Anthrax Treatment

• Doxycycline 100mg IV or PO for 60 days
• Ciprofloxacin 400 mg IV or 500 mg PO q 12 hr for
  60 days
• Pen G 4 million u IV q 4h for 60 days
• Amoxicillin 500 PO q 8 h for 60 days
• Treat based on confirmed exposure
• There is no quick, reliable lab test to diagnose
  an individual patient

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Vancomycin-Resistant Enterococci

• Most common enterococcal infections are cystitis,
  pyelonephritis and prostatitis
• Most enterococci are susceptible to ampicillin,
  nitrofurantoin or quinolones
• Obtain cultures on all serious infections in
  which enterococci are possible etiology

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Vancomycin-Resistant Enterococci (Contd)

• If enterococci are vancomycin-resistant, Synercid
  (quinupristin/dalfopristin) may be used

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Prevention of VRE Infection

• Nosocomial enterococcal infections are spread by
  direct contact
• Private rooms with isolation
• Gloves and gown when entering room
• Disposable instruments and meal trays

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Penicillin-Resistant Strep

• 14 of isolates intermediate resistance (mic
  0.1-1.0)
• 9.5 high level resistance (mic gt2.0)
• Resistance to other antibiotics is increasing and
  is related to penicillin resistance
• Choice of definitive therapy must be guided by
  sensitivity testing

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Empiric Treatment of Penicillin-Resistant Strep

• For community-acquired pneumonia, begin with
  macrolide
• Oral cephalosporins do not have adequate
  bactericidal activity to treat pneumonia caused
  by penicillin-resistant pneumococci
• Very high level resistance treat with
  levofloxacin or gatifloxacin

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West Nile Virus

• First U.S. case seen in 1999
• Belongs to flavivirus group
• Primary amplifying hosts are crows and jays
• Human infection from mosquito bites
• Peak incidence end Aug/early Sept
• Incubation period 2-14 days

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West Nile Virus (Contd)

• Clinical patterns
• Asymptomatic 80 of cases
• West Nile fever 3-6 day self-limited febrile
  illness with flu-like symptoms and sometimes a
  rash
• CNS involvement encephalitis or
  meningoencephalitis- 1.5 of cases
• Diagnosis
• Presence of IgM antibody to WN virus in serum
  and/or CSF
• WN IgM in CSF indicative of CNS involvement since
  IgM doesnt cross blood brain barrier
• Beware of cross-reactivity with other
  flaviviruses

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West Nile Virus (Contd)

• Prognosis
• Advanced age is the most important predictor of
  death gt 70 y.o. at highest risk
• Severe muscle weakness and change in level of
  consciousness risk factors for death from
• encephalitis
• Long-term cognitive and neurologic impairment
  common among encephalitis survivors
• Treatment and Prevention
• Supportive therapy, mosquito repellants and
  community mosquito control programs

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General Management of Infectious Disease

• Get culture and sensitivity whenever possible
• Use narrow spectrum antibiotics at high enough
  doses and for proper duration
• Dont treat a viral infection with antibiotics

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Avoiding Resistance in Hospitalized Patients

• Diagnose the infection with a culture whenever
  possible
• Target the pathogen with the most specific
  antibiotic
• Optimize dose, route, duration
• Dont treat contamination or colonization
• Stop antibiotic when infection is not diagnosed,
  cultures are negative

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Minimize Outpatient Antibiotics

• Treatment may not be needed or can be delayed
  for
• Sinusitis
• Bronchitis
• Otitis
• Use first line drugs in appropriate doses

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Meningitis

• Meningitis typically presents with fever,
  headache, stiff neck, nausea and vomiting
• Stiff neck is NOT required
• Progression from URI to headache and vomiting is
  suspicious
• Meningeal irritation signs are quite sensitive
  and fairly specific
• Consider as medical emergency - time is of the
  essence in diagnosis and treatment

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Physical Signs Which Help to Predict Pathogen in
Meningitis
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Epidemiology of Meningitis
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Influenza

• Typical scenario
• Acute onset fever, chills, myalgias, headache,
  sore throat, cough, severe malaise
• Epidemic activity
• Late fall through early spring
• Serious complications
• Highest among the elderly, the very young and
  those with underlying chronic conditions
• Secondary bacterial pneumonia
• Pneumococcus, S. aureus or H. influenzae

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Treatment of Influenza

• Usually treated symptomatically
• Amantidine and rimantadine are only active
  against influenza A (not B)
• Both are equally effective for Type A
• Zanamivir and oseltamivir are active against both
  Type A and B, but more expensive

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Influenza Prevention

• Annual vaccination is the most effective
  prevention
• Groups to vaccinate over 50 years, children 6-23
  months, chronic pulmonary or cardiac disease,
  diabetes, late pregnancy, health care workers,
  household contacts of high risk persons,
  essential service workers, anyone who wants one

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Fever of Unknown Origin

• Defined as fever of 3 weeks duration that is
  gt38.3 C on several occasions failure to diagnose
  after 3 outpatient visits or 3 days of
  hospitalization
• This functional definition helps exclude acute
  viral illness and most other acute causes as they
  resolve or a source is found

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Work-up for Fever of Unknown Origin

• Document the presence of fever and its
  characteristics
• Thorough history looking at all possible risk
  factors family history, ethnicity, travel
  history, animal exposures
• Repeat history and exam periodically
• Discontinue as many medications as possible, both
  prescription and OTC

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Work-up for Fever of Unknown Origin (Contd)

• History and exam should guide testing
• Serial blood cultures (three over 48 hrs)
• Differential includes infection, neoplasm,
  hypersensitivities, autoimmune diseases
• In elderly, most common are malignancy, collagen
  vascular disease, and lastly occult infection

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Treatment of Fever of Unknown Origin

• Empiric drug trials should be used with caution
  if at all
• If malignancy is suspected, consider a trial of
  naproxen
• Neutropenic patients are the only group in which
  empiric broad spectrum antibiotics should be
  used, such as ceftazidime plus an aminoglycoside

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Sexually Transmitted Diseases
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Urethritis

• Gonococcal urethritis is abrupt in onset with
  copious purulent discharge
• Non-gonoccocal pathogens Chlamydia trachomatis,
  Ureaplasma, Mycoplasma genitalium or Trichomonas
  vaginalis
• Treatment must assume penicillin-resistant
  gonococcus

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Cervicitis

• Purulent or mucopurulent endocervical discharge
• Gram stain gt10 wbc/hpf
• Gram negative intracellular diplococci
• Commonly asymptomatic
• Suprapubic pain and tenderness may mean pelvic
  inflammatory disease

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Treatment of Urethritis and Cervicitis
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Vulvovaginitis

• Candida pruritis, flocculent white discharge, pH
  4.0-4.5, hyphae on KOH prep
• Trichomonas soreness, profuse green-yellow
  discharge, pH 5-6, trichomonads on wet prep
• Bacterial vaginosis often asymptomatic white
  gray discharge, pH gt4.5, amine odor with KOH,
  clue cells on wet prep

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Vaginitis Treatment

• Candidiasis topical azole (eg. miconazole) or
  oral fluconazole 150 mg single dose
• Trichomoniasis metronidazole 500 mg bid x 7 d or
  2 gm single dose
• Bacterial vaginosis metronidazole 500 mg bid x 7
  d or 2 gm single dose clindamycin or
  metronidazole topically

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Pelvic Inflammatory Disease

• Includes endometriosis, salpingitis, tubo-ovarian
  abscess
• Risk factors multiple partners, frequent
  intercourse, new partners within previous 30 days
• Symptoms vaginal discharge, pain, fever
• Exam cervical motion or adnexal tenderness

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Treatment of PID
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Urinary Tract Infections
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Acute Cystitis

• Women and girls older than 2
• Acute onset dysuria, frequency
• Fever is usually not present
• Pyuria gt 5-10 wbc/hpf or positive leukocyte
  esterase
• Positive urine culture
• Most common E. coli, other enterobacteria,
  enterococci, Staph saprophyticus

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Treatment of Acute Cystitis

• Single dose better compliance and less side
  effects but lower cure rate
• Three day better effectiveness than single dose
  as effective as 7-10 day
• TMP/SMX DS bid x 3d or
• Amoxicillin 500 mg tid x 3d or
• Cephalosporin or fluoroquinolone x 3d

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Acute Pyelonephritis

• Fever, chills , flank pain
• Flank or CVA tenderness to percussion
• Positive urine culture, often positive blood
  culture
• Same microbiology as cystitis

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Treatment of Pyelonephritis

• Hospitalized with IV antibiotics vs. outpatient
  with oral antibiotics
• No clear evidence either way
• Low risk patients may be considered for
  outpatient care
• IV therapy ampicillin plus gentamicin or
  tobramycin
• Fluoroquinolone may be used IV or PO

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Prostatitis

• Acute fever, chills, perineal or low back pain,
  dysuria or frequency
• Prostate is extremely tender avoid vigorous exam
  in acute prostatitis because of severe pain and
  risk of causing bacteremia
• Chronic Intermittent episodes of dysuria or
  frequency prostate is enlarged and may be mildly
  tender

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Treatment of Prostatitis

• TMP/SMX DS bid
• Fluoroquinolone
• Doxycycline 100 mg bid
• Acute infection
• Under 35 years old treat for 7 days
• Over 35 years old treat for 1 month
• Chronic infections need 1-3 months of treatment

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Lymphadenopathy

• Small nodes in back of neck, axillae, or groin
  may be normal
• Nodes in other regions, or any node gt1 cm is
  potentially abnormal
• Nodes gt 3 cm suggest malignancy

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LymphadenopathyHistory and Exam

• Confirm mass is a lymph node
• Acute or chronic
• Associated systemic symptoms
• Characteristics firm, soft, tender
• Localized or generalized

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LymphadenopathyDifferential

• Localized - look for infections or malignancy in
  the area which the node drains
• Generalized - systemic infections, AIDS
  toxoplasmosis, leukemia, lymphoma, (Hodgkin's or
  non-Hodgkin's)
• Hilar - sarcoid, carcinoma, tuberculosis, fungal
  infection

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When to Biopsy

• When simpler procedures have failed to give
  diagnosis
• If undiagnosed after weeks to months especially
  if enlarging
• In generalized lymphadenopathy, avoid inguinal
  or axillary node biopsy
• Supraclavicular nodes have best diagnostic yield

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HIV Disease
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HIV Disease

• Caused by a single-stranded RNA retro virus
• Encodes reverse transcriptase which copies the
  genome into the double- stranded DNA which then
  becomes integrated into the host genome

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Epidemiology

• HIV was present in sub-Saharan Africa in the
  1950s
• In the U.S. by 1970
• Now reported in 150 countries
• 920,000 cases and 420,000 deaths through December
  2000
• Greatest increase in spread is in heterosexual
  population

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Transmission

• Transmission by sexual contact , body fluids, and
  perinatally
• High titers in semen and cervical fluid
• Infection facilitated by breaks in epithelium
• Sexual transmission more efficient male to female
• Perinatal transmission as high as 30 in
  untreated pregnancies

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Disease Progression

• Main determinants are CD4 count and viral load
• Absolute CD4 count and rate of decline determine
  need for treatment
• Quantitative titer of circulating HIV RNA is the
  single best predictor of long term progression
• Measured by reverse transcriptase PCR or DNA
  amplification

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Monitoring

• Test for viral load and CD4 every 3-4 months
  until treatment is started
• Begin treatment when CD4 lt350
• After treatment is begun, re-test 4-8 weeks later
  to determine response
• Re-check in 3-4 months
• Once stable, check viral load every 3-4 months

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Constitutional Symptoms

• Acute viral syndrome fever, night sweats,
  anorexia, weight loss
• Early disease (CD4 gt500) similar to non-HIV
• Mid-stage (CD4 200-500) possible TB or STD as
  unrecognized source of fever
• Late disease (CD4 75-200) opportunistic
  infections
• Advanced disease (CD4 lt75) disseminated
  mycobacterium avium and CMV

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CNS Symptoms

• Cognitive dysfunction, decreased level of
  consciousness, delirium, psychosis
• Late disease (CD4 75-200) due to cryptococcal
  meningitis, CMV, HSV, VZV encephalitis, HIV
  dementia
• Advanced disease (CD4 lt75) due to primary CMV or
  advanced HIV dementia

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GI Symptoms

• Dysphagia, odynophagia, food sticking
• Mid-stage - oral thrush
• Late disease- candidal esophagitis, herpes
  simplex (I or II)
• Advanced disease- same as above plus CMV and
  aphthous ulcers
• Diarrhea- common in HIV caused by HIV itself or
  by opportunistic infections

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Skin Manifestations

• Very common affect 90 of HIV patients
• Early disease may be associated with viral
  exanthem, seborrhea, HSV, HPV, staph cellulitis,
  Kaposis sarcoma
• Mid-stage candida, oral hairy leukoplakia,
  atopic dermatitis
• Late-stage above get worse also opportunistic
  fungal infections

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Treatment of HIV Disease

• HIV treatment guidelines are changing rapidly but
  there are some general principles
• Major goals are to suppress viremia and prevent
  immunosupression
• Start treatment only when patient is ready to
  comply
• Treat all symptomatic patients

56
Treatment of HIV Disease (Contd)

• Treat asymptomatic patients when CD4 lt 350 or
  viral load is high (bDNA gt30,000 or PCR gt55,000)
• Monotherapy is NOT recommended
• A combination of 3 antiviral drugs is now
  recommended
• CD4 lt 200 treat with TMP/SMX DS 1 q day to
  prevent Pneumocystis carinii

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Treatment of HIV Disease (Contd)

• Nucleoside analogs - inhibit reverse
  transcriptase interfere with the formation of
  DNA
• Non-nucleoside reverse transciptase inhibitors -
  inhibit reverse transcriptase by a different
  mechanism
• Protease inhibitors - prevent cleavage of viral
  proteins interfere with viral maturation and
  assembly

58
Treatment of HIV Disease (Contd)

• Most common recommended program is two nucleoside
  analogs and one protease inhibitor but this is
  rapidly changing and needs to be individualized
• Treatment Failures
• Non-compliance, erratic compliance
• Drug malabsorption, drug-drug interaction
• True resistance

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Prevention of HIV Disease

• A vaccine is not yet available
• Prevention counseling and post-exposure
  prophylaxis
• IV drug users should enter rehab if not, use
  clean needles and sterile equipment
• Promote safer sexual practices
• Prenatal screening and treatment
• Prevention of occupational exposures

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Tuberculosis

• Dramatic increase in cases since 1985 in
  conjunction with HIV epidemic
• Multi-drug resistant TB ( resistance to
  isoniazid and rifampin) increasingly common
• Fever most common symptom of primary TB, hilar
  adenopathy most common X-ray finding
• Cough, weight loss and fatigue most common
  symptoms of reactivation TB, upper lobe
  infiltrates (apical-posterior segments) most
  common X-ray finding
• CT scanning more sensitive than plain CXR

61
Tuberculosis (Contd)

• PPD skin test conversion occurs 4-7 weeks after
  primary infection
• Positive end-point is induration 48-72 hours
  post-administration
• 5 mm high risk populations (e.g., known
  contact, HIV)
• 10 mm moderate risk populations (e.g., health
  care workers, recent arrivals from endemic
  countries)
• 15 mm populations with no specific risk factors
• Consider two-step test in populations with
  waning reactivity (booster phenomenon)

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Tuberculosis (Contd)

• Rapid nucleic acid assays (NAAs) vs. traditional
  isolation methods
• NAAs confirm diagnosis in 2-7 hours
• Isolation methods confirm in 4-8 weeks
• Treatment protocols
• Susceptible TB INH, rifampin, pyrazinamide,
  ethambutol X 2 mos then INH and rifampin X 4 more
  mos
• Multiple drug resistant TB individualized,
  based on sensitivities, consult TB expert
• Prevention INH X 6-12 mos (monitor liver if
  gt35)
• Pregnancy Tx warranted, may breast feed

63
Cellulitis

• Predisposing factors include venous/lymphatic
  compromise, diabetes, alcoholism
• Systemic toxicity often absent
• Beta-hemolytic strep and Staph aureus most common
  pathogens
• Erysipelas distinct form associated with marked
  swelling and sharply demarcated borders
• Preferred treatment options nafcillin,
  cefazolin, cefalexin, amoxicillin/clavulanate

64
Sepsis

• Represents systemic response to infection
• May or may not be associated with shock or
  multiple organ dysfunction syndrome (MODS)
• Most frequent in middle-aged and elderly patients
• Primary infection remains unidentified in 10 of
  cases
• Presence or absence of positive blood cultures
  does not correlate with outcomes
• Outcome worse for nosocomial vs.
  community-acquired bloodstream infections

65
Sepsis (Contd)

• Most common manifestations of MODS
• ARDS
• Acute renal failure
• DIC
• Mortality of sepsis shock with MODS
• 40-50

66
Septic Shock Treatment

• Support airway/respiration/perfusion (septic
  shock medical emergency)
• Supplemental oxygen
• Intubation/assisted ventilation PEEP
• Aggressive fluid replacement (crystalloid
  colloid)
• Vasopressors/inotropes as indicated
• Low dose steriods
• 50 mg hydrocortisone q6 hr i.v. fludrocortisone
  50 ug once daily x 7 days
• Antibiotics
• Source control is critical targeted intervention
• Beta-lactam aminoglycoside
• Stress ulcer/DVT prophylaxis

67
Septic Shock Treatment (Contd)

• Maximize nutritional support
• Earlier the better
• Favor enteral over parenteral if gut working
• Use supplements rich in branched-chain amino
  acids
• No clear benefit from corticosteroids
• Recombinant human activated protein C
• May be beneficial against coagulation disorders
• Greatest benefit shown in the sickest patients
• Approved dose for septic shock is 24 mcg/kg/hr X
  96 hours at a cost of 5,000-10,000 per course
• Side effects include serious bleeding events

68
Dermatophyte (Tinea) Infections

• Most common cause of superficial fungal infection
• Increased susceptibility in immunocompromised
  patients
• Tinea capitis and onychomycosis most difficult to
  treat

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Tinea Capitis

• Black dot most common form in U.S.
• Enlarging, erythematous, scaling patch(es)
  progressing to alopecia
• Scalp hairs break off flush with surface
• Detritus in follicles appears as black dots
• No fluorescence, in contrast to less common gray
  patch type

70
Tinea Capitis Treatment

• Micronized griseofulvin preferred 250 mg PO QD
  X 6-12 wks, 10 mg/kg QD X 6-12 wks in children
• Topical treatment futile
• Kerion requires addition of Staph antibiotic
• Identification of asymptomatic carriers important
  treat with selenium sulfide shampoo

71
Onychomycosis

• Caused by dermatophytes, non-dermatophytes, and
  yeast
• Distal subungual type most common form
  (Trichophyton rubrum)
• Nail dystrophies can mimic, so confirm diagnosis
  with KOH or culture

72
Onychomycosis Treatment

• Terbinafine (preferred) 250 mg QD X 6 wks
  (fingernails), 250 mg QD X 12 weeks (toenails)
• Itraconazole fixed 200 mg QD X 8 wks
  (fingernails), 200 mg QD X 12 wks pulse 400 mg
  QD 1 wk/4 X 2 mos (fingernails), 400 mg QD 1
  wk/4 X 3 mos (toenails)
• Nail lacquer (ciclopirox) for mild to moderate
  disease without lunular involvement only, slow
  acting, works in only 1 in 15 patients
• Check liver enzymes before starting PO
  antifungals
• For standard dosing protocols, no need to follow
  LFTs unless Hx of liver problems

73
Infectious Diarrhea

• Salmonella leading cause of foodborne illness in
  U.S. (poultry, eggs, dairy products)
• Shigella second leading cause
• Campylobacter associated with undercooked
  infected poultry, enterohemorrhagic E. coli with
  undercooked ground beef
• Rotavirus and Norwalk agents common viral causes
  (rotavirus predominantly in infants)
• Cyclospora newly identified small bowel path-
  ogen, intense fatigue and malaise a hallmark

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Infectious Diarrhea General Work-up

• Sensitivity/specificity of fecal leukocytes only
  70 and 50, respectively
• Standard stool cultures not indicated unless Sx
  last gt5-7 days, patient toxic, or for public
  health purposes
• Clinical context usually obviates need for
  rotavirus and C. difficile tests

75
Infectious Diarrhea Approach to Treatment

• Antibiotic therapy usually not indicated due to
  self-limited course
• Rehydration/maintaining hydration top priority
• Avoid anti-motility agents if fever and/or bloody
  diarrhea
• No evidence that transition diets make a
  difference (e.g. BRAT)
• Transient lactose intolerance sometimes occurs

76
Pseudomembranous Colitis

• Most cases due to Clostridium difficile
• Can occur 1-3 weeks after stopping an antibiotic
• Nosocomial diarrhea usually C. difficile
• Responds to course of metronidazole

77
Travelers Diarrhea

• Usual agent is enterotoxigenic E. coli
• Hi risk areas Asia, Africa, South/Central
  America, Mexico
• Usual onset 5-15 days after arrival
• Prophylaxis not recommended
• Prevention avoid ice cubes, fruit salads,
  lettuce, chicken salads, condiments on table,
  steam table buffets
• Treatment for mild cases, fluids only add
  ciprofloxin 500 mg BID X 3 days and loperamide
  for moderate to severe cases