Board Review Infectious Diseases. Exposure History Southwest US: Coccidioidomycosis Southwest US: Coccidioidomycosis Midwest US: Histoplasmosis Midwest.

Board Review Infectious Diseases

Exposure History Southwest US: Coccidioidomycosis Southwest US: Coccidioidomycosis Midwest US: Histoplasmosis Midwest US: Histoplasmosis Parrots/exotic birds: Psittacosis Parrots/exotic birds: Psittacosis Cat: Pasteurella, Toxo-, Bartonella Cat: Pasteurella, Toxo-, Bartonella Rats: Plague, Lepto, Hanta- Rats: Plague, Lepto, Hanta- Pigeons: Cryptococcus Pigeons: Cryptococcus

Exposure History Turtles/IguanasSalmonella Turtles/IguanasSalmonella TicksRMSF, Lyme, Ehrlichia, Babesia TicksRMSF, Lyme, Ehrlichia, Babesia RabbitsTularemia RabbitsTularemia ShellfishVibrio, Hepatitis A ShellfishVibrio, Hepatitis A Sheep/CattleQ fever Sheep/CattleQ fever Goat CheeseBrucella Goat CheeseBrucella HamburgersE Coli 0157 HamburgersE Coli 0157

Exposure History Antibiotic useC. difficile Antibiotic useC. difficile Hot tubPseudomonas folliculitis Hot tubPseudomonas folliculitis MAC pneumonitis MAC pneumonitis ShowersLegionnaires ShowersLegionnaires Gardening/RosesSporothrix Gardening/RosesSporothrix MosquitoesMalaria, Arboviruses, MosquitoesMalaria, Arboviruses, West Nile Virus West Nile Virus Chicken coopHistoplasma Chicken coopHistoplasma

Viral Infections

West Nile Virus Culex Mosquito Bite Culex Mosquito Bite Cases: transfusion, organ transplant Cases: transfusion, organ transplant Peak time in August Peak time in August Usually a non-specific febrile illness Usually a non-specific febrile illness 1/150: Meningitis, encephalitis, flaccid paralysis 1/150: Meningitis, encephalitis, flaccid paralysis CSF: lymphocytic predominance CSF: lymphocytic predominance Dx: IgM+ serum&CSF; PCR CSF Dx: IgM+ serum&CSF; PCR CSF May have elevated lipase May have elevated lipase Tx: Supportive Tx: Supportive ?interferon alfa 3N, ?IVIG ?interferon alfa 3N, ?IVIG Deaths in elderly, diabetics Deaths in elderly, diabetics Long-term neuropsych complaints Long-term neuropsych complaints Prevention: DEET; no vaccine Prevention: DEET; no vaccine

Rabies History of a bite History of a bite Incubation 20-90 days (as long as 20 yrs) Incubation 20-90 days (as long as 20 yrs) Symptoms: Symptoms: Local parasthesias Local parasthesias Encephalitis Encephalitis Hydrophobia, Aerophobia Hydrophobia, Aerophobia Death: Clinical disease is always fatal Death: Clinical disease is always fatal Tx: Supportive; avoid transmission via saliva Tx: Supportive; avoid transmission via saliva

Clinical Rabies

Rabies: Diagnosis Suspect clinically Suspect clinically Confirmation: Confirmation: Brain examination Brain examination Skin biopsy at nape of the neck Skin biopsy at nape of the neck Techniques: Techniques: Histopath: Negri bodies Histopath: Negri bodies DFA DFA Reverse transcription polymerase chain reaction (RT-PCR) - saliva, CSF, or tissue Reverse transcription polymerase chain reaction (RT-PCR) - saliva, CSF, or tissue

Negri Body

Rabies: Treatment Clinical Disease: Clinical Disease: None confirmed None confirmed Case in St. Louis treated with induced coma, ribavirin Case in St. Louis treated with induced coma, ribavirin Coenzyme Q10, l-arginine, and vitamin C also were administered in an attempt to replenish neurotransmitter substrates Coenzyme Q10, l-arginine, and vitamin C also were administered in an attempt to replenish neurotransmitter substrates MMWR, December 24, 2004 / 53(50);1171-1173

Rabies: Treatment Before clinical disease: Before clinical disease: Post-exposure: Post-exposure: Vaccine and HRIG (HRIG only if no hx of vaccination) Vaccine and HRIG (HRIG only if no hx of vaccination) HRIG: 1/2 at wound & 1/2 IM HRIG: 1/2 at wound & 1/2 IM Vaccine at a different site Vaccine at a different site Cleanse wound Cleanse wound Pre-exposure: Pre-exposure: Rabies vaccine in 3 shots for those at risk- vets, spelunkers, 3 rd world travelers for >3mos Rabies vaccine in 3 shots for those at risk- vets, spelunkers, 3 rd world travelers for >3mos Following animal bite give 2 boosters Following animal bite give 2 boosters

Rabies Post-exposure Prophylaxis Animal bites Animal bites Bats, raccoon, fox, skunk, coyote: treat with rabies vaccine & HRIG (different sites) Bats, raccoon, fox, skunk, coyote: treat with rabies vaccine & HRIG (different sites) Domestic cat/dog: observe for 10 days or brain examination; hold therapy unless evidence that animal is rabid Domestic cat/dog: observe for 10 days or brain examination; hold therapy unless evidence that animal is rabid Other animals: livestock, squirrels, rodents, rabbits, chipmunks, hamsters- almost never rabid; therapy generally not recommended; check with P.H. Other animals: livestock, squirrels, rodents, rabbits, chipmunks, hamsters- almost never rabid; therapy generally not recommended; check with P.H.

Bats Most common animal exposure associated with rabies in the US Most common animal exposure associated with rabies in the US Most patients DO NOT recall a bite Most patients DO NOT recall a bite Simply exposure to a bat without actual evidence of a bite should be treated Simply exposure to a bat without actual evidence of a bite should be treated Finding a bat in the room of a child should be treated Finding a bat in the room of a child should be treated

Bite Management Consider the need for tetanus immunization Consider the need for tetanus immunization Leave the wound open; avoid sutures or wound closure Leave the wound open; avoid sutures or wound closure Consider antibiotics for prevention of wound infection (Augmentin, Unasyn) Consider antibiotics for prevention of wound infection (Augmentin, Unasyn)

Herpesviruses VZV VZV HSV 1 and 2 HSV 1 and 2 CMV CMV HHV6 HHV6 HHV8 HHV8

Antivirals for Herpes Acyclovir, valacyclovir, famciclovir, penciclovir Acyclovir, valacyclovir, famciclovir, penciclovir Valtrex most bioavailable Valtrex most bioavailable Risks: nephrotoxicity, seizures (with incr Cr), TTP/HUS with high doses of valtrex in HIV patients Risks: nephrotoxicity, seizures (with incr Cr), TTP/HUS with high doses of valtrex in HIV patients Resistance: decreased thymidine kinase activity Resistance: decreased thymidine kinase activity Idoxuridine, trifluridine; flomivirsen Idoxuridine, trifluridine; flomivirsen Topical; HSV keratitis; flomivirsen for CMV retinitis Topical; HSV keratitis; flomivirsen for CMV retinitis Ganciclovir Ganciclovir Side effects: kidney dysfunction, neutropenia Side effects: kidney dysfunction, neutropenia Foscarnet Foscarnet Does not require thymidine kinase Does not require thymidine kinase Kidney function, electrolytes Kidney function, electrolytes Cidofovir Cidofovir Nephrotoxic Nephrotoxic

Varicella zoster virus Chickenpox & shingles Chickenpox & shingles Transmission: Transmission: Respiratory secretions/direct contact Respiratory secretions/direct contact Incubation: Incubation: 9-21 days 9-21 days Hence med student who is VZV neg and is exposed to case, should avoid work from days 9-21 especially if working in heme/onc ward Hence med student who is VZV neg and is exposed to case, should avoid work from days 9-21 especially if working in heme/onc ward

VZV Adults with chickenpox Adults with chickenpox Higher risk for PNA, hepatitis, and encephalitis Higher risk for PNA, hepatitis, and encephalitis Tx: adults (>12 yrs): acyclovir 800 mg 5x/d x 7 days Tx: adults (>12 yrs): acyclovir 800 mg 5x/d x 7 days Administer within 24 hrs of rash Administer within 24 hrs of rash Decreases symptoms x 1 day Decreases symptoms x 1 day Complicated disease, immunocompromised, 3 rd trimester: use IV acyclovir 10 mg/kg q8 for 5-7 d Complicated disease, immunocompromised, 3 rd trimester: use IV acyclovir 10 mg/kg q8 for 5-7 d DX: clinical; IFA or culture of lesion DX: clinical; IFA or culture of lesion VZV negative adults should receive varicella vaccine VZV negative adults should receive varicella vaccine Pregnant women and immunocompromised s/p exposure: give VRIG within 96 hours; some would also begin acyclovir Pregnant women and immunocompromised s/p exposure: give VRIG within 96 hours; some would also begin acyclovir

Chickenpox

VZV Shingles Shingles Vesicles in dermatomal pattern Vesicles in dermatomal pattern DX: clinical; can perform IFA / cx of lesion DX: clinical; can perform IFA / cx of lesion TX: antiviral (Valtrex) within 72 hrs (esp. in age>50, severe pain, or facial/eye involvement) TX: antiviral (Valtrex) within 72 hrs (esp. in age>50, severe pain, or facial/eye involvement) Speeds initial recovery; no data on PHN effect Speeds initial recovery; no data on PHN effect Steroids: controversial; decreases acute pain Steroids: controversial; decreases acute pain PHN: big issue; esp age>50 yrs PHN: big issue; esp age>50 yrs Try local tx, pain meds, elavil, anti-seizure meds Try local tx, pain meds, elavil, anti-seizure meds Immunocompromised with >1 dermatome: IV acyclovir Immunocompromised with >1 dermatome: IV acyclovir Vaccination of elderly: Vaccination of elderly: ZOSTAVAX is indicated for prevention of shingles in individuals >60 years ZOSTAVAX is indicated for prevention of shingles in individuals >60 years

Shingles Herpes viruses resistant to acyclovir are treated with foscarnet

HSV1/2 Orolabial Orolabial 1 day of valtrex 1 day of valtrex ACV for 5-7 days ACV for 5-7 days Healing 1 day faster Healing 1 day faster Genital Genital Valtrex for 3 days Valtrex for 3 days ACV for 7 days ACV for 7 days Other: Herpes gladiatorum (wrestlers), whitlow (HCW) Other: Herpes gladiatorum (wrestlers), whitlow (HCW) Treat with any of the 3 agents Treat with any of the 3 agents Keratitis: oral agent plus topical Keratitis: oral agent plus topical CNS or immunocompromised with widespread disease CNS or immunocompromised with widespread disease IV Acyclovir IV Acyclovir Resistant herpes: foscarnet Resistant herpes: foscarnet Prophylaxis: > 6 episodes/year: ACV 800 po daily Prophylaxis: > 6 episodes/year: ACV 800 po daily

Cytomegalovirus Retinitis Retinitis AIDS patients CD4<50 AIDS patients CD4<50 Valganciclovir, fomivirsen Valganciclovir, fomivirsen Disseminated disease Disseminated disease Transplant patients, HIV patients Transplant patients, HIV patients Colitis, pneumonia, etc. Colitis, pneumonia, etc. Pp65 antigenemia, PCR positive Pp65 antigenemia, PCR positive Tx: valganciclovir or iv ganciclovir Tx: valganciclovir or iv ganciclovir

Smallpox Variola virus; last case in 1978 in Somalia Variola virus; last case in 1978 in Somalia Recent threat is due to bioterrorism Recent threat is due to bioterrorism Group of patients seeking care for unexplained skin lesions, sepsis, respiratory illness, etc. Group of patients seeking care for unexplained skin lesions, sepsis, respiratory illness, etc. Clinical: Clinical: Oral enanthem occurs 1 st Oral enanthem occurs 1 st Vesicles beginning on face and spread distally to legs/arms including palms/soles (trunk is relatively spared) Vesicles beginning on face and spread distally to legs/arms including palms/soles (trunk is relatively spared) Lesions are firm, nodular Lesions are firm, nodular All lesions in the same stage of disease All lesions in the same stage of disease Incubation - 14 days Incubation - 14 days Diagnosis: fluid from vesicle Diagnosis: fluid from vesicle

Smallpox Tx: Supportive Tx: Supportive Consider cidofovir Consider cidofovir Vaccination if within 4 days of exposure Vaccination if within 4 days of exposure Mortality - 30% Mortality - 30% Prevention: Prevention: Glove/gowns/mask in isolated negative pressure room Glove/gowns/mask in isolated negative pressure room Vaccinate contacts within 4 days of exposure Vaccinate contacts within 4 days of exposure Consider specific immune globulin for contacts who cannot receive the vaccine Consider specific immune globulin for contacts who cannot receive the vaccine Pre-exposure vaccination: avoid in immunocompromised, pregnancy, ezcema Pre-exposure vaccination: avoid in immunocompromised, pregnancy, ezcema

Smallpox

Eczema vaccinatum “Smallpox shot infects soldier's toddler son Boy critically ill; mom also stricken” Treatment: vaccinia immune globulin, or VIG. He also received cidofovir and the experimental drug ST-246

Hantavirus Pulmonary Syndrome Sin Nombre virus Sin Nombre virus Four Corners/Southwest US Four Corners/Southwest US Exposure to rodents (Peromyscus-deer mouse) via inhalation of saliva/excreta Exposure to rodents (Peromyscus-deer mouse) via inhalation of saliva/excreta Acute fever, HA, cough, low platelets and non- cardiogenic pulmonary edema, leading to respiratory failure Acute fever, HA, cough, low platelets and non- cardiogenic pulmonary edema, leading to respiratory failure

Hantavirus Pulmonary Syndrome Dx: IFA of sputum or serology Dx: IFA of sputum or serology Clues to Dx: Clues to Dx: Hemoconcentration Hemoconcentration Low Platelets Low Platelets Immunoblasts on smear Immunoblasts on smear Tx: Supportive; 40% mortality Tx: Supportive; 40% mortality No evidence for the use ribavirin No evidence for the use ribavirin

Influenza Winter months Winter months Incubation: 48 hrs Incubation: 48 hrs Sxs: Fevers, headache, pharyngitis and severe body aches Sxs: Fevers, headache, pharyngitis and severe body aches Signs: conjunctivitis, nasal d/c, pharynx inflammation Signs: conjunctivitis, nasal d/c, pharynx inflammation Secondary infections: Strep pneumoniae or Staph aureus (MRSA) Secondary infections: Strep pneumoniae or Staph aureus (MRSA)

Influenza Children: Reye’s Syndrome (Avoid ASA) Children: Reye’s Syndrome (Avoid ASA) Dx: Dx: Clinically with local influenza activity Clinically with local influenza activity Confirm dx with rapid testing (culture takes too long) Confirm dx with rapid testing (culture takes too long) Tx: Tx:-Symptomatically

Influenza - Antiviral therapy: - Give <48 hours of onset, fever/cough, known community cases - Reduces symptom duration by 50 % (1-2 days) Medication Choices: Medication Choices: Amantadine and rimantadine: only for type A Amantadine and rimantadine: only for type A Side effects: insomnia, anxiety, change MS, not in pregnancy Side effects: insomnia, anxiety, change MS, not in pregnancy Rimantidine – less side effects and better efficacy Rimantidine – less side effects and better efficacy Amantidine – adjust dose if CrCl<50 Amantidine – adjust dose if CrCl<50 Rimantidine – adjust dose with liver dysfunction Rimantidine – adjust dose with liver dysfunction

Influenza Treatment cont. Treatment cont. Neurominidase inhibitors: Neurominidase inhibitors: Effect against types A, B and avian H5N1 Effect against types A, B and avian H5N1 Oseltamivir (oral) – may cause GI side effects Oseltamivir (oral) – may cause GI side effects Zanamivir (inhaler)- may induce bronchospasm Zanamivir (inhaler)- may induce bronchospasm Useful for both influenza A & B Useful for both influenza A & B Treat for 5 days Treat for 5 days

Influenza Prophylaxis Influenza in community and unvaccinated person- Influenza in community and unvaccinated person- Give short course of antiviral medication Give short course of antiviral medication Influenza in a nursing facility Influenza in a nursing facility Chemoprophylaxis to all resident for duration of outbreak and for 1 week thereafter Chemoprophylaxis to all resident for duration of outbreak and for 1 week thereafter Use of amantidine/rimantidine to treat outbreak cases, use neuroaminidase inhibitor for prophylaxis Use of amantidine/rimantidine to treat outbreak cases, use neuroaminidase inhibitor for prophylaxis Resistance to amantadine/rimantidine can occur within 2-3 days of therapy Resistance to amantadine/rimantidine can occur within 2-3 days of therapy

Influenza: Prevention Vaccination indicated for: Vaccination indicated for: >50 years >50 years Chronic medical conditions Chronic medical conditions Health care workers Health care workers Family members of those with med condition Family members of those with med condition Institutionalized Institutionalized Pregnancy - 2 nd -3 rd trimesters during the flu season Pregnancy - 2 nd -3 rd trimesters during the flu season Children on chronic ASA Children on chronic ASA

H5N1 Avian Influenza Most cases with direct contact with poultry Most cases with direct contact with poultry Symptoms: Symptoms: Typical influenza-like symptoms (e.g., fever, cough, sore throat, and muscle aches) to eye infections (conjunctivitis), pneumonia, acute respiratory distress Typical influenza-like symptoms (e.g., fever, cough, sore throat, and muscle aches) to eye infections (conjunctivitis), pneumonia, acute respiratory distress Treatment: oseltamivir Treatment: oseltamivir

Severe Acute Respiratory Syndrome (SARS) Coronavirus Coronavirus China China Civet cats Civet cats Bilateral PNA/hypoxia Bilateral PNA/hypoxia Diagnosis: culture Diagnosis: culture Treatment: ?ribavirin in trials Treatment: ?ribavirin in trials Positive pressure ventilation Positive pressure ventilation

Parvovirus B19 Child: Fifth’s disease with ‘slapped cheeks’ Child: Fifth’s disease with ‘slapped cheeks’ Adult Adult Sickle cell, etc.: aplastic crisis Sickle cell, etc.: aplastic crisis HIV: chronic anemia HIV: chronic anemia Pregnant: hydrops fetalis Pregnant: hydrops fetalis Immunocompetent: arthritis (esp women), rash Immunocompetent: arthritis (esp women), rash Transmission: Transmission: Respiratory, blood, congenital Respiratory, blood, congenital

Parvovirus B19 Dx: Dx: Immunocompetent: serology IgM Immunocompetent: serology IgM Immunocompromised: PCR Immunocompromised: PCR BMB: pronormoblasts BMB: pronormoblasts Tx: Tx: Supportive Supportive Severe anemia: IVIG Severe anemia: IVIG Arthritis: NSAIDS Arthritis: NSAIDS

Acute HIV Infection Consider in sexually active with ‘mono’ like illness Consider in sexually active with ‘mono’ like illness May have false positive monospot or CMV IgM May have false positive monospot or CMV IgM Dx: HIV viral load (>10,000) Dx: HIV viral load (>10,000) ELISA may initially be negative ELISA may initially be negative Tx: Consider beginning HAART; no absolute guideline Tx: Consider beginning HAART; no absolute guideline

Viral Transmission Needlestick Injury Needlestick Injury Hepatitis B30% Hepatitis B30% Hepatitis C3% Hepatitis C3% HIV0.3% HIV0.3% “Rule of Three’s” “Rule of Three’s”

Tick Bites

Ticks S/p tick bite: S/p tick bite: Empiric therapy only in endemic area with observed nymphal partially engorged deer tick – doxycycline 200 mg x 1 given within 72 hours of exposure Empiric therapy only in endemic area with observed nymphal partially engorged deer tick – doxycycline 200 mg x 1 given within 72 hours of exposure Otherwise, do not give prophylaxis Otherwise, do not give prophylaxis Hard Ticks: Hard Ticks: Ixodes: Lyme, Babesia, HGE (risk of coinfection) Ixodes: Lyme, Babesia, HGE (risk of coinfection) Dermacentor: RMSF, Tularemia, Tick paralysis Dermacentor: RMSF, Tularemia, Tick paralysis Amblyomma: HME, RMSF, Tularemia Amblyomma: HME, RMSF, Tularemia Soft Ticks: Soft Ticks: Ornithodoros: Relapsing Fever Ornithodoros: Relapsing Fever

Babesia B. microti B. microti Transmission: Transmission: Tick bite by Ixodes dammini Tick bite by Ixodes dammini Blood transfusion Blood transfusion Nantucket Island, Martha’s vineyard, Shelter Island, Wisconsin, Washington State Nantucket Island, Martha’s vineyard, Shelter Island, Wisconsin, Washington State Sxs: HA, fevers, myalgias Sxs: HA, fevers, myalgias Can cause overwhelming infection in asplenic patients Can cause overwhelming infection in asplenic patients

Babesia Labs: hemolytic anemia, low plts, increased creatinine Labs: hemolytic anemia, low plts, increased creatinine Dx: parasites on smear “Maltese cross” Dx: parasites on smear “Maltese cross” Tx: Tx: Atovaquone and azithromycin (fewer side effects): now the preferred agents Atovaquone and azithromycin (fewer side effects): now the preferred agents Quinine and clindamycin is the alternate regimen Quinine and clindamycin is the alternate regimen Severe disease: exchange transfusion Severe disease: exchange transfusion

Babesia

Lyme Disease #1 Vector borne disease in US #1 Vector borne disease in US Borrelia burgdorferi Borrelia burgdorferi Ixodes tick bite Ixodes tick bite Most do NOT remember tick bite Most do NOT remember tick bite Tick must be on for >24-36 hrs for infection Tick must be on for >24-36 hrs for infection Northern US/ New England States, Minnesota, CA Northern US/ New England States, Minnesota, CA “Martha’s Vineyard” “Martha’s Vineyard” “Nantucket” “Nantucket”

Lyme Disease Incubation 7-10 days Incubation 7-10 days Early manifestations: Early manifestations: Erythema migrans (in 60-80%) - ‘bulls eye’ Erythema migrans (in 60-80%) - ‘bulls eye’ Fever, HA, arthralgias, adenopathy Fever, HA, arthralgias, adenopathy

Lyme Disease Disseminated disease Disseminated disease Symptoms: Weeks-Months Symptoms: Weeks-Months Multiple skin lesions Multiple skin lesions Arthritis Arthritis AV Block/myocarditis AV Block/myocarditis Neuro: Neuro: Aseptic meningitis Aseptic meningitis Facial palsy –bilateral Facial palsy –bilateral Foot drop Foot drop Cases of MRI lesions c/w neoplasia Cases of MRI lesions c/w neoplasia

Lyme Disease Late Disease: Years Late Disease: Years Monoarticular arthritis (knee #1 joint) Monoarticular arthritis (knee #1 joint) Chronic neurologic symptoms Chronic neurologic symptoms polyneuropathy polyneuropathy memory loss memory loss depression depression somnolence somnolence

Lyme Disease Diagnosis: Diagnosis: Most important is clinical: presence of EM makes the diagnosis in an endemic area Most important is clinical: presence of EM makes the diagnosis in an endemic area ELISA: IgM in 4 weeks; early on is negative and is non-specific ELISA: IgM in 4 weeks; early on is negative and is non-specific Use Western blot for confirmation (Definitive Diagnosis!) Use Western blot for confirmation (Definitive Diagnosis!) PCR- synovial fluid or CSF PCR- synovial fluid or CSF Hx of LYMErix: false-positive ELISA Hx of LYMErix: false-positive ELISA Use Western Blot Use Western Blot

Lyme Disease Treatment: Treatment: Doxycycline 100mg bid x 14-21days Doxycycline 100mg bid x 14-21days Alternatives: amox-, cefuroxime, azithro- Alternatives: amox-, cefuroxime, azithro- Ceftriaxone for CV/Neuro (except facial palsy with neg LP or 1 st degree block-can use doxy) Ceftriaxone for CV/Neuro (except facial palsy with neg LP or 1 st degree block-can use doxy) For post-Lyme syndromes: no benefit of ABX For post-Lyme syndromes: no benefit of ABX 2 controlled trials 2 controlled trials There is NO benefit to months of IV ABX There is NO benefit to months of IV ABX Prevention Prevention Daily tick checks Daily tick checks

RMSF R. rickettsii R. rickettsii Suspect in TN, OK, NC, SC Suspect in TN, OK, NC, SC Cases recently in Arizona: vector R. sanguineus Cases recently in Arizona: vector R. sanguineus Sxs: fever, myalgia, HA followed by rash on wrists/ankles (from distal to trunk) Sxs: fever, myalgia, HA followed by rash on wrists/ankles (from distal to trunk) Dx: low plts, low WBC, high LFT’s Dx: low plts, low WBC, high LFT’s Make dx clinically and treat; confirm with serology or IFA of skin; Make dx clinically and treat; confirm with serology or IFA of skin; Avoid Weil-Felix test Avoid Weil-Felix test Tx: Doxycycline 100 mg bid x 7 days Tx: Doxycycline 100 mg bid x 7 days

Ehrlichiosis “Spotless RMSF” (No rash in most cases) “Spotless RMSF” (No rash in most cases) Tick bite (April-Sept) Tick bite (April-Sept) HGE (Human Granulocytic Ehrlichiosis) HGE (Human Granulocytic Ehrlichiosis) Anaplasma (Erlichia) phagocytophilium Anaplasma (Erlichia) phagocytophilium Ixodes Tick Ixodes Tick Northeast and west coast Northeast and west coast

Ehrlichiosis HME (Human Monocytic Ehrlichiosis) HME (Human Monocytic Ehrlichiosis) E. chaffeensis E. chaffeensis Lone Star Tick Lone Star Tick Southeast US Southeast US

Ehrlichiosis Symptoms: Symptoms: HA, fever, N/V, malaise, arthralgias (3-7 day incubation); rash in 36% of HME HA, fever, N/V, malaise, arthralgias (3-7 day incubation); rash in 36% of HME Labs: Labs: Morulae in leukocytes (esp in HGE) Morulae in leukocytes (esp in HGE) Elevated LFT’s, thrombocytopenia, leukopenia Elevated LFT’s, thrombocytopenia, leukopenia Diagnosis: Clinical; IFA, serology Diagnosis: Clinical; IFA, serology Treatment: Doxycycline 100mg bid x 7-14 days Treatment: Doxycycline 100mg bid x 7-14 days

Tularemia Ticks, contact, inhalation or ingestion Ticks, contact, inhalation or ingestion RABBIT hunting in SE U.S. RABBIT hunting in SE U.S. Potential bioterrorism agent: pneumonic Potential bioterrorism agent: pneumonic Most common: ulceroglandular Most common: ulceroglandular Dx: serology; GNR=F. tularensis Dx: serology; GNR=F. tularensis Tx: Gentamicin/streptomycin Tx: Gentamicin/streptomycin Standard precautions Standard precautions Post-exposure prophylaxis: cipro or doxy Post-exposure prophylaxis: cipro or doxy

Tick paralysis Ascending paralysis (looks like GBS) Ascending paralysis (looks like GBS) ALWAYS search patient for a tick ALWAYS search patient for a tick especially at hairline especially at hairline Treatment is prompt removal Treatment is prompt removal

Anthrax Pulmonary: Incubation 1-6 days Pulmonary: Incubation 1-6 days Fever, malaise, cough and mild chest discomfort, rapidly followed by severe respiratory distress with labored breathing, sweating, and bluish or gray skin. No coryza; Widened mediastinum! Hemoconcentration. Fever, malaise, cough and mild chest discomfort, rapidly followed by severe respiratory distress with labored breathing, sweating, and bluish or gray skin. No coryza; Widened mediastinum! Hemoconcentration. Shock and death within 24-36 hours of severe disease Shock and death within 24-36 hours of severe disease 50% develop hemorrhagic meningitis 50% develop hemorrhagic meningitis Cutaneous Cutaneous Black eschar surrounded by swelling; painless Left untreated the local infection may progress into bacteremia and death (20%). With treatment, fatalities are rare Black eschar surrounded by swelling; painless Left untreated the local infection may progress into bacteremia and death (20%). With treatment, fatalities are rare GI: GI: Oropharyngeal infection (pseudomembrane), bloody diarrhea Oropharyngeal infection (pseudomembrane), bloody diarrhea

Anthrax

Anthrax Dx: GPR’s on specimens

Anthrax Post-exposure: Post-exposure: FQ x 60 days (alternative: doxycycline) FQ x 60 days (alternative: doxycycline) Cutaneous: Cutaneous: FQ x 60 days FQ x 60 days GI or Pulmonary: GI or Pulmonary: FQ and Clinda and Rif x 60 days FQ and Clinda and Rif x 60 days Meningitis: Meningitis: Cipro, clinda, and vanco (perhaps rifampin) Cipro, clinda, and vanco (perhaps rifampin) Switch to amoxicillin/penicillin if organism is sensitive Switch to amoxicillin/penicillin if organism is sensitive Avoid cephalosporins/Septra/macrolides Avoid cephalosporins/Septra/macrolides No person-to-person transmission; use standard precautions No person-to-person transmission; use standard precautions

Botulism Foodborne, infant, wound (black tar heroin) Foodborne, infant, wound (black tar heroin) Cranial nerve palsies, respiratory failure, descending flaccid paralysis Cranial nerve palsies, respiratory failure, descending flaccid paralysis D’s: diplopia, dystonia, dysphagia, dysarthria, descending paralysis D’s: diplopia, dystonia, dysphagia, dysarthria, descending paralysis Dx: clinical; mouse neutralization test Dx: clinical; mouse neutralization test EEG: reduced, but normal, action potentials EEG: reduced, but normal, action potentials Tx: Antitoxin, penicillin Tx: Antitoxin, penicillin Debride wounds Debride wounds No specific isolation No specific isolation

Leptospirosis Worldwide; very common in Hawaii Worldwide; very common in Hawaii Contact with contaminated water (associated with animal urine) Contact with contaminated water (associated with animal urine) Incubation: 10 days Incubation: 10 days Myalgias (calf), fever, headache, conjunctival suffusion, palatal exanthem Myalgias (calf), fever, headache, conjunctival suffusion, palatal exanthem Renal/hepatic (Weil’s), bleeding, pulmonary (hemorrhage), meningitis are potential complications Renal/hepatic (Weil’s), bleeding, pulmonary (hemorrhage), meningitis are potential complications

Leptospirosis Diagnosis: Diagnosis: Clinical Clinical Swimming in a pool near livestock Swimming in a pool near livestock Serology Serology Treatment: PCN G or ceftriaxone or doxycycline Treatment: PCN G or ceftriaxone or doxycycline Prophylaxis in military study with doxycycline 200mg q week. Prophylaxis in military study with doxycycline 200mg q week.

Rat Bite Fever Bite from a rat Streptobacillus moniliformis Hemorrhagic palmar rash Arthritis Flu-like illness Rx with PCN

Plague Yersinia pestis Yersinia pestis 3 forms: 3 forms: Bubonic (fleas) Bubonic (fleas) Pneumonic (inhalation) Pneumonic (inhalation) Septicemic Septicemic Tx: Streptomycin Tx: Streptomycin Contact and droplet precautions Contact and droplet precautions

Parasites

Malaria Organisms P. falciparum (tropical) P. falciparum (tropical) Banana gametocytes, multiple infected rbc’s Banana gametocytes, multiple infected rbc’s P. vivax (temperate – Latin America, Asia) P. vivax (temperate – Latin America, Asia) P. ovale (W. Africa, Indonesia, New Guinea, Philippines) P. ovale (W. Africa, Indonesia, New Guinea, Philippines) Oval shape, infects reticulocytes Oval shape, infects reticulocytes P. malariae (SE Asia and India) P. malariae (SE Asia and India) Band and basket forms Band and basket forms

Clinical Manifestations Chills, fever and sweats Chills, fever and sweats Headache, myalgias, backache, nausea, dizziness, diarrhea, abdominal pain and cough Headache, myalgias, backache, nausea, dizziness, diarrhea, abdominal pain and cough Symptoms every 48-72 (malariae) hours Symptoms every 48-72 (malariae) hours Atypical presentation Atypical presentation Prophylactic meds or partial immunity Prophylactic meds or partial immunity ALWAYS suspect in returning traveler with fevers ALWAYS suspect in returning traveler with fevers

Complications P. falciparum P. falciparum Cerebral malaria, severe anemia, ARDS (vascular permeability changes), lactic acidosis, DIC, renal failure –“blackwater fever”, hypoglycemia, splenomegaly Cerebral malaria, severe anemia, ARDS (vascular permeability changes), lactic acidosis, DIC, renal failure –“blackwater fever”, hypoglycemia, splenomegaly P. vivax P. vivax Splenic rupture Splenic rupture P. malariae P. malariae Immune complex glomerulonephritis Immune complex glomerulonephritis

Diagnosis Giemsa smears Giemsa smears Smears every 8 hours for 2-3 days (obtain during febrile episodes) Smears every 8 hours for 2-3 days (obtain during febrile episodes) Thick (identification of parasite) and thin (species determination) smears Thick (identification of parasite) and thin (species determination) smears Rule out concomitant infections Rule out concomitant infections HIV, bacteremia, typhoid, etc. HIV, bacteremia, typhoid, etc. Malaria does not cause eosinophilia! Malaria does not cause eosinophilia!

Treatment Treat all symptomatic cases with a positive smear Treat all symptomatic cases with a positive smear If the species cannot be determined or if there is a dual infection, treat for P. falciparum If the species cannot be determined or if there is a dual infection, treat for P. falciparum Consider resistance patterns when determining the appropriate therapy Consider resistance patterns when determining the appropriate therapy

Chloroquine-susceptible P. vivax, ovale, malariae CQ 1g (600mg-base) PO x 1, then 500mg in 6 hours, then 500mg qd for a total of 25mg/kg of base CQ 1g (600mg-base) PO x 1, then 500mg in 6 hours, then 500mg qd for a total of 25mg/kg of base Primaquine 30 mg base PO qd x 14 days for P. vivax/ovale to treat the liver stage Primaquine 30 mg base PO qd x 14 days for P. vivax/ovale to treat the liver stage Check G6PD status Check G6PD status P. vivax/ovale may be CQ resistant in Papua, New Guinea, and Indonesia: quinine & doxy P. vivax/ovale may be CQ resistant in Papua, New Guinea, and Indonesia: quinine & doxy

Chloroquine-susceptible P. falciparum Locations Locations West of the Panama Canal, Mexico, Dominican Republic and Haiti are considered CQ sensitive West of the Panama Canal, Mexico, Dominican Republic and Haiti are considered CQ sensitive Most of the Middle East also remain sensitive except Yemen, Oman and Iran Most of the Middle East also remain sensitive except Yemen, Oman and Iran

CQ-resistant P. falciparum Quinine sulfate 650mg PO q8 and doxycycline 100 mg po bid x 7 days. Quinine sulfate 650mg PO q8 and doxycycline 100 mg po bid x 7 days. Resistance described in Thailand Resistance described in Thailand Malarone (atovaquone/proguanil) 400 mg x 3 d Malarone (atovaquone/proguanil) 400 mg x 3 d Mefloquine 15mg base/kg PO x 1, then 10 mg/dg x 1 in 12 hours Mefloquine 15mg base/kg PO x 1, then 10 mg/dg x 1 in 12 hours Artemisins may be used for resistant strains Artemisins may be used for resistant strains

Monitoring Effective therapy Effective therapy Reduction in the level of parasitemia by >/=75% in 48 hours Reduction in the level of parasitemia by >/=75% in 48 hours Complete clearance by 7 days Complete clearance by 7 days G6PD status before primaquine G6PD status before primaquine Pregnancy test Pregnancy test

Other Malarial Therapies Severe disease: quinidine gluconate iv and doxy/clinda Severe disease: quinidine gluconate iv and doxy/clinda Exchange Transfusions Exchange Transfusions Parasite count of >/=10% or >5% with severe organ dysfunction Parasite count of >/=10% or >5% with severe organ dysfunction Cerebral malaria Cerebral malaria Avoid steroids Avoid steroids Seizures Seizures Use standard anticonvulsants, control temperature and treat hypoglycemia Use standard anticonvulsants, control temperature and treat hypoglycemia

Prevention Chemoprophylaxis: Chemoprophylaxis: No medication is 100% No medication is 100% Quinolines: 2 weeks before to 4 weeks after returning from an endemic area (Mefloquine, CQ) Quinolines: 2 weeks before to 4 weeks after returning from an endemic area (Mefloquine, CQ) Doxycycline: 2 days before departure, and continued for 4 weeks after. (Drug of choice in Thailand) Doxycycline: 2 days before departure, and continued for 4 weeks after. (Drug of choice in Thailand) Malarone: 1 day before travel and 1 week after Malarone: 1 day before travel and 1 week after Avoid mefloquine with hx seizures, psych disorders or conduction abnormalities Avoid mefloquine with hx seizures, psych disorders or conduction abnormalities Pregnancy: best option is CQ or mefloquine (depending on area) Pregnancy: best option is CQ or mefloquine (depending on area) Use CQ in areas that are susceptible; otherwise use mefloquine (not in Thailand) or doxycycline or malarone Use CQ in areas that are susceptible; otherwise use mefloquine (not in Thailand) or doxycycline or malarone

Leishmaniasis Sandfly bite Sandfly bite SA, Africa, India, Middle East SA, Africa, India, Middle East Cutaneous: ulcerative lesion of face/arm Cutaneous: ulcerative lesion of face/arm Mucocutaneous: New World; L. braziliensis Mucocutaneous: New World; L. braziliensis Visceral (Kala azar): Fevers, pancytopenia, gammaglobulinemia; dx BMB, liver or LN bx Visceral (Kala azar): Fevers, pancytopenia, gammaglobulinemia; dx BMB, liver or LN bx Tx: Tx: Visceral: antimony (India: amphotericin) Visceral: antimony (India: amphotericin) Mucocutaneous: antimony Mucocutaneous: antimony Cutaneous: antimony (fluconazole for L. major) Cutaneous: antimony (fluconazole for L. major)

Chagas Disease Trypanosomiasis Trypanosomiasis Central/South America Central/South America Reduviid bug ‘kissing’ Reduviid bug ‘kissing’ Romana’s sign Romana’s sign Megacolon, achalasia, CV (CHF, block) Megacolon, achalasia, CV (CHF, block) Tx: Tx: acute: nifurtimox acute: nifurtimox chronic: manage sxs chronic: manage sxs

Strongyloides Larva enters via skin Larva enters via skin SE U.S. and developing countries SE U.S. and developing countries Usually asymptomatic, eosinophilia Usually asymptomatic, eosinophilia Hyperinfection in immunosuppressed: Hyperinfection in immunosuppressed: PNA, meningitis, GNR bacteremia PNA, meningitis, GNR bacteremia Tx: Ivermectin Tx: Ivermectin

Neurocysticercosis CNS lesion(s) in a young patient with seizures CNS lesion(s) in a young patient with seizures Mexican or lives near Mexican border Mexican or lives near Mexican border Most common parasitic infection of the central nervous system Most common parasitic infection of the central nervous system Dx: serology Dx: serology Tx: “viable cysts”: steroids, albendazole, surgery for localized lesion Tx: “viable cysts”: steroids, albendazole, surgery for localized lesion

Neurocysticercosis

Travel #1 issue: traveler’s diarrhea #1 issue: traveler’s diarrhea Prophylaxis generally not recommended Prophylaxis generally not recommended If diarrhea develops: imodium & FQ If diarrhea develops: imodium & FQ Campy from SE Asia are FQ resistant – use Azithromycin Campy from SE Asia are FQ resistant – use Azithromycin #1 vaccine preventable disease: Hepatitis A #1 vaccine preventable disease: Hepatitis A 2 shot vaccine (0, 6 mos) 2 shot vaccine (0, 6 mos) Need 2 weeks for protection to develop Need 2 weeks for protection to develop Hepatitis E: Especially severe in pregnancy Hepatitis E: Especially severe in pregnancy Yellow fever: live vaccine Yellow fever: live vaccine Parts of Africa and South America Parts of Africa and South America

Travel African tick bite fever African tick bite fever #1 Rickettsial infection worldwide #1 Rickettsial infection worldwide Rural safari Rural safari Amblyomma bite Amblyomma bite Fever, LNs, rash, single eschar at bite Fever, LNs, rash, single eschar at bite Doxycycline or FQ Doxycycline or FQ Dengue Dengue Central/South America, Caribbean Central/South America, Caribbean Aedes mosquito bite Aedes mosquito bite Headache, myalgias, fever, petechiae, low WBC and platelets Headache, myalgias, fever, petechiae, low WBC and platelets Supportive Care Supportive Care

TB Inhalation of droplet nuclei Inhalation of droplet nuclei Primary disease: Ghon focus and complex Primary disease: Ghon focus and complex Bacilli may spread hematogenously Bacilli may spread hematogenously Nodes, kidneys, epiphyses of the long bones, joints, vertebrae, meninges (base of brain- CN palsies) and the apical posterior areas of the lung Nodes, kidneys, epiphyses of the long bones, joints, vertebrae, meninges (base of brain- CN palsies) and the apical posterior areas of the lung New risk: infliximab New risk: infliximab Before TNF alpha blocker initiation: check ppd Before TNF alpha blocker initiation: check ppd

PPD Screening test of choice Screening test of choice Negative test does NOT r/o disease Negative test does NOT r/o disease Takes 3-12 weeks to become positive after exposure Takes 3-12 weeks to become positive after exposure IGNORE prior BCG vaccine history IGNORE prior BCG vaccine history Quantiferon assay can be utilized Quantiferon assay can be utilized Patient exposure: check ppd at baseline and repeat in 12 weeks Patient exposure: check ppd at baseline and repeat in 12 weeks Progression to disease: Progression to disease: 10% lifetime risk of disease (1/2 in first 2yrs) 10% lifetime risk of disease (1/2 in first 2yrs) 10% yearly risk in HIV+ 10% yearly risk in HIV+

PPD 5mm: 5mm: HIV+, close recent contact of TB case, positive CXR c/w old TB, immunosuppression HIV+, close recent contact of TB case, positive CXR c/w old TB, immunosuppression 10mm: 10mm: From high prevalence areas in the last 5 years, IVDA’s, congregate settings (nursing home, prison, etc), children less than 4 years old, mycobacteriology lab personnel, and others with high risk of progression (med conditions) From high prevalence areas in the last 5 years, IVDA’s, congregate settings (nursing home, prison, etc), children less than 4 years old, mycobacteriology lab personnel, and others with high risk of progression (med conditions) 15 mm: 15 mm: No risk factors No risk factors No benefit for anergy testing No benefit for anergy testing

Treatment of Latent Infection INH 300 mg po qd for 9 months INH 300 mg po qd for 9 months B6 10-50mg/day in those at risk B6 10-50mg/day in those at risk Pregnancy, seizure history, HIV, diabetes, alcohol abuse Pregnancy, seizure history, HIV, diabetes, alcohol abuse Rifampin x 4 months as an alternative Rifampin x 4 months as an alternative RIF/PZA for 2 months RIF/PZA for 2 months Not recommended due to liver toxicity Not recommended due to liver toxicity

Treatment of Active TB Four drug therapy Four drug therapy Where INH resistance is 4% or greater Where INH resistance is 4% or greater Standard regimen: Standard regimen: RIF/INH/PZA/EMB x 2 months, then INH/RIF x 4 months RIF/INH/PZA/EMB x 2 months, then INH/RIF x 4 months For HIV patients: same regimen For HIV patients: same regimen Substitute rifabutin in patients on PIs/NNRTIs Substitute rifabutin in patients on PIs/NNRTIs For extrapulmonary: same regimen For extrapulmonary: same regimen

TB: Key Points Never add a single drug to a failing regimen Never add a single drug to a failing regimen Rule out active disease before giving INH prophylaxis Rule out active disease before giving INH prophylaxis Be aware of possibility of MDR Be aware of possibility of MDR Use at least 2-3 drug that are sensitive Use at least 2-3 drug that are sensitive

TB Drug Side Effects INH: hepatitis (ALT-resolves rapidly), peripheral neuropathy, GI upset INH: hepatitis (ALT-resolves rapidly), peripheral neuropathy, GI upset RIF: reduced OCP efficacy, hepatitis (cholestatic picture), orange secretions RIF: reduced OCP efficacy, hepatitis (cholestatic picture), orange secretions PZA: hepatitis (ALT-resolves slowly), rash, hyperuricemia (gout is uncommon) PZA: hepatitis (ALT-resolves slowly), rash, hyperuricemia (gout is uncommon) EMB: optic neuritis EMB: optic neuritis STREP: ototoxicity and nephrotoxicity STREP: ototoxicity and nephrotoxicity

Other Mycobacteria Slow growers Rapid growers MAC M. fortuitum M. kansasii M. chelonae/abscessus, smegmatis

MAC Pulmonary Pulmonary Most common in those with COPD Most common in those with COPD Indolent upper-lobe disease Indolent upper-lobe disease Middle-lobe disease in elderly females Middle-lobe disease in elderly females hx of MVP or pectus excavatum hx of MVP or pectus excavatum Disseminated disease Disseminated disease HIV with CD4<50 HIV with CD4<50 FUO, anemia, high alk phos, nodes, diarrhea FUO, anemia, high alk phos, nodes, diarrhea Lymphadenitis Lymphadenitis Hypersensitivity pneumonitis: hot tub-associated Hypersensitivity pneumonitis: hot tub-associated Treatment Treatment Clarithromycin and ETB +/- rifabutin Clarithromycin and ETB +/- rifabutin

Other Mycobacteria M. kansasii M. kansasii Lung cavitation Lung cavitation RIE (PZA-resistant) RIE (PZA-resistant) Rapid growers: Rapid growers: Skin infections Skin infections CF/bronchiectasis: superinfection CF/bronchiectasis: superinfection

+AFB Mycobacteria: TB, MAC, M. marinum, and all mycobacteria species Mycobacteria: TB, MAC, M. marinum, and all mycobacteria species Nocardia: weakly + (modified AFB) Nocardia: weakly + (modified AFB) GI pathogens GI pathogens Cryptosporidium Cryptosporidium Isospora Isospora

Granulocytopenia Infection rate correlates with degree of neutropenia (ANC<200) and duration Infection rate correlates with degree of neutropenia (ANC<200) and duration Infection usually originates in oropharynx, skin, or GI tract Infection usually originates in oropharynx, skin, or GI tract Daily PE’s are crucial Daily PE’s are crucial Neutropenic precautions: hand washing, no fresh fruits/vegetables, no ill contacts Neutropenic precautions: hand washing, no fresh fruits/vegetables, no ill contacts

Granulocytopenia Air filtration for BMT patients (Aspergillus) Air filtration for BMT patients (Aspergillus) Prophylaxis for Neutropenics: Prophylaxis for Neutropenics: Quinolones decreases GNR infections and in a meta-analysis improved survival Quinolones decreases GNR infections and in a meta-analysis improved survival

Neutropenic Fever Organisms: Organisms: Bacteria (GPC’s are the most common: Staph, Strep) GNR’s. Candida, Aspergillus, Nocardia, etc. Bacteria (GPC’s are the most common: Staph, Strep) GNR’s. Candida, Aspergillus, Nocardia, etc. Antibiotic coverage: Antibiotic coverage: Anti-Pseudomonal ß lactam and aminoglycoside Anti-Pseudomonal ß lactam and aminoglycosideOR Ceftazidime, Cefepime, Imipenum-cilastatin, or meropenem Ceftazidime, Cefepime, Imipenum-cilastatin, or meropenem **Low-risk patient: cipro plus augmentin **Low-risk patient: cipro plus augmentin

Neutropenic Fever: Add Vancomycin: Add Vancomycin: catheter infection, mucositis, known MRSA colonization, shock, blood cx with GP, hx. of fluoroquinolone use catheter infection, mucositis, known MRSA colonization, shock, blood cx with GP, hx. of fluoroquinolone use Fever for 3-5 days: Add an antifungal Fever for 3-5 days: Add an antifungal Ampho vs. caspo vs. vori vs. itra Ampho vs. caspo vs. vori vs. itra Pulmonary disease: rapid bronchoscopy to find causative agent Pulmonary disease: rapid bronchoscopy to find causative agent

Bacterial Infections

Bites Human: Viridians strep (#1), Eikenella, Bacteroides, other anaerobes Human: Viridians strep (#1), Eikenella, Bacteroides, other anaerobes Tx: Augmentin; Copious irrigation Tx: Augmentin; Copious irrigation PCN allergy: clinda and cipro PCN allergy: clinda and cipro If wound appears infected, IV therapy with Unasyn or Zosyn If wound appears infected, IV therapy with Unasyn or Zosyn Xrays for clench fist injuries; consider iv abx and admission. Consult hand surgeon Xrays for clench fist injuries; consider iv abx and admission. Consult hand surgeon

Bites Animal: Pasteurella multocida Animal: Pasteurella multocida Dog: Capnocytophaga (DF2) Dog: Capnocytophaga (DF2) In patients with splenectomy may develop local eschar with DIC/sepsis In patients with splenectomy may develop local eschar with DIC/sepsis

Bites Treat animal bites with Augmentin Treat animal bites with Augmentin PCN allergic: doxycycline or cipro/clinda, septra/clinda PCN allergic: doxycycline or cipro/clinda, septra/clinda Always instruct to elevate the extremity Always instruct to elevate the extremity Consider rabies and Td shots Consider rabies and Td shots Don’t suture potential infected wounds Don’t suture potential infected wounds Remember: Remember: Pasteurella is resistant to diclox, cephalexin, clinda and erythro! Pasteurella is resistant to diclox, cephalexin, clinda and erythro! Cipro works in vitro Cipro works in vitro

Other skin findings Vesicle or ulcer on finger of health care worker: Whitlow: HSV (tx acyclovir) Vesicle or ulcer on finger of health care worker: Whitlow: HSV (tx acyclovir) Dishwasher: Candida Dishwasher: Candida Recurrent furuncles: S. aureus/MRSA nasal colonization Recurrent furuncles: S. aureus/MRSA nasal colonization Ecythma gangrenosum: Pseudomonas Ecythma gangrenosum: Pseudomonas

Whitlow

Cellulitis #1 Organisms=Group A Strep or S. aureus #1 Organisms=Group A Strep or S. aureus Diagnosis is clinical; not by aspiration Diagnosis is clinical; not by aspiration Unique Exposures: Unique Exposures: Seawater: Vibrio vulnificus Seawater: Vibrio vulnificus Increased risk in cirrhosis/immunocompromised- hemorrhagic bullae with bacteremic/sepsis Increased risk in cirrhosis/immunocompromised- hemorrhagic bullae with bacteremic/sepsis Also found in shellfish! Also found in shellfish! Fishtank: Mycobacterium marinum Fishtank: Mycobacterium marinum

Cellulitis Unique Exposures: Unique Exposures: Hot tub: Pseudomonas Hot tub: Pseudomonas Fresh-water exposure: Aeromonas Fresh-water exposure: Aeromonas Gas in tissues: Clostridium perfringens Gas in tissues: Clostridium perfringens Tx: diclox/1st gen cephalosporin for most cases of cellulitis Tx: diclox/1st gen cephalosporin for most cases of cellulitis Consider Vanco IV given the MRSA rates with significant SSTIs Consider Vanco IV given the MRSA rates with significant SSTIs Consider clindamycin: more effective due to protein synthesis inhibition Consider clindamycin: more effective due to protein synthesis inhibition Use GNR drugs depending on exposure Use GNR drugs depending on exposure

Cellulitis Recurrent: Recurrent: Usually due to anatomic defect Usually due to anatomic defect Arm: mastectomy Arm: mastectomy Leg: CABG Leg: CABG R/o DVT, arterial insufficiency, anatomic defect, tinea pedis, etc. R/o DVT, arterial insufficiency, anatomic defect, tinea pedis, etc. Prophylactic ABX for repeated episodes Prophylactic ABX for repeated episodes Amoxicillin po Amoxicillin po Penicillin IM Penicillin IM

Community Acquired MRSA Young, healthy persons Young, healthy persons Recurrent soft tissue infections or furunculosis Recurrent soft tissue infections or furunculosis Peds: necrotizing pneumonia Peds: necrotizing pneumonia PVL gene positive PVL gene positive Sensitive to most non-β-lactam antibiotics Sensitive to most non-β-lactam antibiotics IV: Vancomycin, daptomycin, tigecycline IV: Vancomycin, daptomycin, tigecycline PO: Septra, minocycline, rifampin, linezolid PO: Septra, minocycline, rifampin, linezolid Be careful with clindamycin due to inducible resistance (D test) Be careful with clindamycin due to inducible resistance (D test) Decrease colonization: ?mupirocin, phisohex Decrease colonization: ?mupirocin, phisohex Check nares culture Check nares culture NOT an immunodeficiency problem NOT an immunodeficiency problem

Necrotizing Fasciitis Group A Strep, S. aureus and Clostridium perfringens (+gas) most commonly cited on tests Group A Strep, S. aureus and Clostridium perfringens (+gas) most commonly cited on tests Also can be polymicrobial: esp Fournier’s gangrene Also can be polymicrobial: esp Fournier’s gangrene Back tar heroin: C. sordellii Back tar heroin: C. sordellii Exam: pain out of proportion, dusky, crepitant swelling, bullae, systemic toxicity Exam: pain out of proportion, dusky, crepitant swelling, bullae, systemic toxicity Elevated wbc, ESR, CK Elevated wbc, ESR, CK

Necrotizing Fasciitis Diagnosis is clinical; Never let a diagnostic test (ie MRI) interfere with prompt ABX and surgical debridement Diagnosis is clinical; Never let a diagnostic test (ie MRI) interfere with prompt ABX and surgical debridement Tx: #1 is Surgery; can perform frozen section in OR if in doubt Tx: #1 is Surgery; can perform frozen section in OR if in doubt ABX: ABX: Zosyn + Vanco +/- Gent Zosyn + Vanco +/- Gent PCN and Clindamycin for Group A Strep PCN and Clindamycin for Group A Strep Clindamycin inhibits protein/toxin synthesis Clindamycin inhibits protein/toxin synthesis

Group A Strep Toxic Shock Syndrome Toxic Shock Syndrome 1. Isolation of Group A strep & 1. Isolation of Group A strep & 2. Hypotension (SBP<90mmHg) & 2. Hypotension (SBP<90mmHg) & 3. Two of the following 3. Two of the following Renal insufficiency -Soft tissue necrosis Renal insufficiency -Soft tissue necrosis Coagulopathy/DIC -Rash Coagulopathy/DIC -Rash LFT’s>2x normal LFT’s>2x normal ARDS ARDS

GAS Toxic Shock Syndrome Increase in virulent Group A strep infections Increase in virulent Group A strep infections Most commonly occurs with necrotizing fasciitis Most commonly occurs with necrotizing fasciitis Prompt diagnosis Prompt diagnosis Tx: PCN and Clindamycin Tx: PCN and Clindamycin IVIG IVIG Close contacts: No screening indicated Close contacts: No screening indicated HCWs when >2 cases in 6-months: screen and prophylaxis if positive culture HCWs when >2 cases in 6-months: screen and prophylaxis if positive culture

Other Causes of TSS S. aureus S. aureus Associated with tampons, wounds, burns Associated with tampons, wounds, burns Rx: Vancomycin and IVIG Rx: Vancomycin and IVIG If MSSA: oxacillin or nafcillin If MSSA: oxacillin or nafcillin Clostridium sordellii Clostridium sordellii Post-abortion, use of mifepristone Post-abortion, use of mifepristone PCN and Clindamycin PCN and Clindamycin

Sepsis Syndrome Definitions: Definitions: SIRS SIRS 2 or more: T>38 or 90, RR>20, wbc>12 or 10% bands 2 or more: T>38 or 90, RR>20, wbc>12 or 10% bands Sepsis: SIRS with a confirmed infectious etiology Sepsis: SIRS with a confirmed infectious etiology Severe sepsis: Sepsis with organ dysfunction or hypoperfusion Severe sepsis: Sepsis with organ dysfunction or hypoperfusion Septic shock: sepsis-induced hypotension not responsive to fluid resuscitation Septic shock: sepsis-induced hypotension not responsive to fluid resuscitation

Sepsis Syndrome Treatment: Treatment: Fluids Fluids Correct underlying disease process Correct underlying disease process Disproportionate shock: Addisons, bleeding? Disproportionate shock: Addisons, bleeding? Antibiotics: carbapenem and vancomycin Antibiotics: carbapenem and vancomycin

Sepsis Syndrome Treatment: Treatment: Activated protein C Activated protein C Reduced mortality from 31% to 25% Reduced mortality from 31% to 25% Use only with severe sepsis (APACHE>24) and no contraindications (increased risk of bleeding) Use only with severe sepsis (APACHE>24) and no contraindications (increased risk of bleeding) Low-dose steroids Low-dose steroids Low baseline and <9 mcg/dl after cosyntropin stim test Low baseline and <9 mcg/dl after cosyntropin stim test Tight glucose control Tight glucose control

Osteomyelitis Hematogenous Hematogenous Uncommon in Adults Uncommon in Adults S. aureus involving the vertebrae (#1) S. aureus involving the vertebrae (#1) Sickle Cell=Salmonella Sickle Cell=Salmonella IVDA=Pseudomonas in SI or clavicular joint IVDA=Pseudomonas in SI or clavicular joint Point tenderness, referred pain Point tenderness, referred pain Dx Xrays usually normal; negative bone scan r/o osteo-, MRI defines abscesses as well Dx Xrays usually normal; negative bone scan r/o osteo-, MRI defines abscesses as well

Osteomyelitis Dx: Dx: Blood cultures frequently positive (67%) Blood cultures frequently positive (67%) Do not rely on sinus drainage for culture Do not rely on sinus drainage for culture Except for perhaps S. aureus Except for perhaps S. aureus Bone biopsy is procedure of choice Bone biopsy is procedure of choice Tx: Oxacillin or Ancef (suspect S. aureus) Tx: Oxacillin or Ancef (suspect S. aureus) Broader coverage for other organisms Broader coverage for other organisms Surgery necessary in chronic osteo- remove necrotic bone Surgery necessary in chronic osteo- remove necrotic bone Treatment = 6 wks of I.V. (8 or more for vertebral) Treatment = 6 wks of I.V. (8 or more for vertebral)

Osteomyelitis Contiguous: Contiguous: Trauma, decubs, diabetic foot, etc. Trauma, decubs, diabetic foot, etc. Probe to bone confirms dx of osteomyelitis Probe to bone confirms dx of osteomyelitis Polymicrobial in many cases Polymicrobial in many cases Nail puncture through shoe=Pseudomonas Nail puncture through shoe=Pseudomonas R/o vascular insufficiency (if +, then revascularize) R/o vascular insufficiency (if +, then revascularize) Tx Zosyn+Vanco/debridement Tx Zosyn+Vanco/debridement

Diabetic Foot Prevention Prevention Screen with monofilament test Screen with monofilament test Podiatry eval / Daily feet inspection Podiatry eval / Daily feet inspection Good BS control Good BS control Yearly checks for peripheral pulses; early referral for vascular eval if not palpable Yearly checks for peripheral pulses; early referral for vascular eval if not palpable

Diabetic Foot Dx: Is there osteomyelitis?? Dx: Is there osteomyelitis?? Probe to bone? Probe to bone? Bone scans usually positive due to surrounding inflammation; Wbc scan or MRI may help Bone scans usually positive due to surrounding inflammation; Wbc scan or MRI may help Cultures from bone (not drainage which is unreliable) Cultures from bone (not drainage which is unreliable)

Prosthetic Joint Infections Staph epi #1 organism Staph epi #1 organism Loosening of joint, pain, drainage, fever; presentation is usually chronic Loosening of joint, pain, drainage, fever; presentation is usually chronic Dx: aspiration or I&D for organism Dx: aspiration or I&D for organism Tx: Tx: Gold standard is joint removal and iv antibiotics for 6 wks then replace hardware Gold standard is joint removal and iv antibiotics for 6 wks then replace hardware Use rifampin with hardware retention Use rifampin with hardware retention Consider debridement with ABX if early infection Consider debridement with ABX if early infection +/- ABX impregnated beads +/- ABX impregnated beads

Septic Arthritis Consider GC Consider GC Especially in young, sexually-active patient Especially in young, sexually-active patient Tenosynovitis, dermatitis, asymmetric polyarthritis Tenosynovitis, dermatitis, asymmetric polyarthritis Tap joint Tap joint Culture mucosal sites Culture mucosal sites Most sensitive is cervix/urethral cx Most sensitive is cervix/urethral cx Treatment: Ceftriaxone x 2 wks Treatment: Ceftriaxone x 2 wks Does not require OR surgical drainage Does not require OR surgical drainage Other causes: S. aureus, other GPCs, GNRs Other causes: S. aureus, other GPCs, GNRs Culture, drain, IV ABX for 3-4 weeks Culture, drain, IV ABX for 3-4 weeks Culture before ABX are begun Culture before ABX are begun

Cardiovascular Infections Diagnostic study of choice=blood cultures (3 sets over 24 hours) Diagnostic study of choice=blood cultures (3 sets over 24 hours) TEE better than TTE TEE better than TTE Esp for detecting vegetations, perivalvular extension, prosthetic IE, and for S. aureus bacteremia vs. IE (cost effective; 25% will have IE: can use 2 vs. 4 wks of antibiotics if TEE is negative) Esp for detecting vegetations, perivalvular extension, prosthetic IE, and for S. aureus bacteremia vs. IE (cost effective; 25% will have IE: can use 2 vs. 4 wks of antibiotics if TEE is negative)

IE Duke’s criteria: Duke’s criteria: Definite: 2 major, 1 major/3 minor or 5 minor Definite: 2 major, 1 major/3 minor or 5 minor Possible: 1 major/1minor or 3 minor Possible: 1 major/1minor or 3 minor Major: Typical organism for 2 blood cx & Major: Typical organism for 2 blood cx & Endocardial involvement (ECHO, PE) Endocardial involvement (ECHO, PE) Minor: Heart condition/IVDA, fever, vascular phen (Janeway, hemorrhages), immunologic phen (Osler’s, GN, Roth spots, RF), serologic/blood cx not in major criteria Minor: Heart condition/IVDA, fever, vascular phen (Janeway, hemorrhages), immunologic phen (Osler’s, GN, Roth spots, RF), serologic/blood cx not in major criteria

Endocarditis #1 organism on a native valve= Strep viridians #1 organism on a native valve= Strep viridians Drug addicts= S. aureus Drug addicts= S. aureus Prosthetic valve= early: S. epidermidis; late: strep/enterococcus Prosthetic valve= early: S. epidermidis; late: strep/enterococcus Culture Negative IE: Culture Negative IE: HACEK: HACEK: HemophilusEikenella HemophilusEikenella Actinobacillus Kingella Actinobacillus Kingella Cardiobacterium Cardiobacterium Q fever, fungi, Brucella, psittacosis, Bartonella, Legionella Q fever, fungi, Brucella, psittacosis, Bartonella, Legionella Underlying conditions: Underlying conditions: Degenerative valves, MVP, bicuspid aortic v. Degenerative valves, MVP, bicuspid aortic v. No longer rheumatic fever No longer rheumatic fever

Endocarditis Strep bovis or Clostridium septicum: Strep bovis or Clostridium septicum: r/o GI cancer with endoscopy r/o GI cancer with endoscopy Acute stroke in the young: r/o endocarditis Acute stroke in the young: r/o endocarditis

Endocarditis Treatment Treat cases of definite and possible IE Treat cases of definite and possible IE Native Valve Native Valve Strep viridians/bovis Strep viridians/bovis PCN or CTX x 4 wks or with gent x 2 wks PCN or CTX x 4 wks or with gent x 2 wks If MIC 0.1-0.5: PCN x 4wks plus gent x 2wks If MIC 0.1-0.5: PCN x 4wks plus gent x 2wks Enterococcus: PCN and Gent x 4 wks Enterococcus: PCN and Gent x 4 wks MSSA: Nafcillin or oxacillin x 4-6 wks; gent x 3-5 days MSSA: Nafcillin or oxacillin x 4-6 wks; gent x 3-5 days MRSA: Vanco x 4-6 wks MRSA: Vanco x 4-6 wks HACEK: Ceftriaxone x 4 wks HACEK: Ceftriaxone x 4 wks ? Cause: Vanco and gent x 4 wks. ? Cause: Vanco and gent x 4 wks. Prosthetic Valve Prosthetic Valve Add Rifampin Add Rifampin

Endocarditis Treatment Total duration 4-6 weeks Total duration 4-6 weeks 2 weeks for right-sided S. aureus IE associated with IVDA 2 weeks for right-sided S. aureus IE associated with IVDA May continue anticoagulation in patients requiring it’s use (i.e., Prosthetic valves) May continue anticoagulation in patients requiring it’s use (i.e., Prosthetic valves)

Endocarditis Treatment Surgery: #1 indication is CHF Surgery: #1 indication is CHF Conduction abnormality, abscess, recurrent embolic events or recurrent bacteremia Conduction abnormality, abscess, recurrent embolic events or recurrent bacteremia Early prosthetic valve IE (<2 months) requires surgery Early prosthetic valve IE (<2 months) requires surgery

Endocarditis Prophylaxis Prophylaxis only recommended if the patient has both a heart condition and a procedure that requires ABX coverage Prophylaxis only recommended if the patient has both a heart condition and a procedure that requires ABX coverage Some experts have debated the utility of prophylaxis as most cases of IE not related to a specific procedure Some experts have debated the utility of prophylaxis as most cases of IE not related to a specific procedure

Endocarditis Prophylaxis High Risk High Risk Prosthetic valve Prosthetic valve Previous IE Previous IE Complex cyanotic congenital lesions Complex cyanotic congenital lesions Moderate Risk Moderate Risk Acquired valve abnormality Acquired valve abnormality HOCM HOCM MVP MVP Other congenital abnormality Other congenital abnormality

Endocarditis Prophylaxis NOT Recommended: NOT Recommended: ASD ASD CABG/catherization CABG/catherization Pacemaker/Defibrillator Pacemaker/Defibrillator MVP with no murmur or regurgitant flow on echo MVP with no murmur or regurgitant flow on echo

Endocarditis Prophylaxis: Recommended Procedures Dental Dental Cleaning, extractions, peridontal procedures Cleaning, extractions, peridontal procedures Respiratory Respiratory T&A, rigid bronchoscopy, surgery of mucosa T&A, rigid bronchoscopy, surgery of mucosa

Endocarditis Prophylaxis: Recommended Procedures GU GU Prostate, cystoscopy, urethral dilation Prostate, cystoscopy, urethral dilation GI GI Sclerotherapy, esoph dilation, ERCP, surgery of the on/through the mucosa Sclerotherapy, esoph dilation, ERCP, surgery of the on/through the mucosa

Endocarditis Prophylaxis NOT Recommended Dental Dental Adjustment of orthodontics, filling cavities Adjustment of orthodontics, filling cavities Resp Resp ETT, flexible bronchoscopy ETT, flexible bronchoscopy GU GU Vaginal hysterectomy, foley, IUD, D&C Vaginal hysterectomy, foley, IUD, D&C GI GI TEE, EGD with or without biopsy TEE, EGD with or without biopsy

Prophylactic Treatments Upper Respiratory/Dental: Upper Respiratory/Dental: Amoxicillin 1 hour before procedure Amoxicillin 1 hour before procedure PCN-allergic: clindamycin 1 dose before PCN-allergic: clindamycin 1 dose before On PCN antibiotics already: use Clindamycin On PCN antibiotics already: use Clindamycin NPO: Ampicillin iv NPO: Ampicillin iv

Prophylactic Treatments GI/GU GI/GU High Risk: Amp/Gent 30min before procedure High Risk: Amp/Gent 30min before procedure High Risk with PCN-allergy: Vanco/Gent High Risk with PCN-allergy: Vanco/Gent Moderate Risk: Amox or Ampicillin Moderate Risk: Amox or Ampicillin Moderate Risk with PCN-allergy: Vanco Moderate Risk with PCN-allergy: Vanco

Myocarditis Think Coxsackievirus B Think Coxsackievirus B Acute CHF in young following URI Acute CHF in young following URI Endomyocardial biopsy not recommended Endomyocardial biopsy not recommended Indication is for dx of heart transplant rejection Indication is for dx of heart transplant rejection R/o Trypanosoma cruzi (Chagas) in endemic area R/o Trypanosoma cruzi (Chagas) in endemic area

Rheumatic fever Reemergence with overcrowding/military Reemergence with overcrowding/military May follow Group A Strep pharyngitis May follow Group A Strep pharyngitis Strep pharyngitis: RF or GN Strep pharyngitis: RF or GN Skin infection: GN Skin infection: GN

Rheumatic fever Major Jones Criteria Major Jones Criteria Carditis, polyarthritis, chorea, EM, nodules Carditis, polyarthritis, chorea, EM, nodules Minor Jones Criteria Minor Jones Criteria Arthralgias, fever, ESR, CRP, prolonged P-R interval on EKG Arthralgias, fever, ESR, CRP, prolonged P-R interval on EKG 2 Major or 1 major and 2 minor for the diagnosis WITH +strep culture or ASO 2 Major or 1 major and 2 minor for the diagnosis WITH +strep culture or ASO

Rheumatic fever Treatment: Treatment: Salicylates Salicylates Steroids for carditis especially with CHF Steroids for carditis especially with CHF Secondary prophylaxis to prevent recurrent events and prevent transmission: Benzathine PCN G 1.2 mU IM monthly Secondary prophylaxis to prevent recurrent events and prevent transmission: Benzathine PCN G 1.2 mU IM monthly

Rheumatic fever Primary Prophylaxis: Primary Prophylaxis: Treat Group A Strep pharyngitis with PCN x 10 days within 10 days of onset Treat Group A Strep pharyngitis with PCN x 10 days within 10 days of onset

Nosocomial Infections Top 4: Top 4: UTI #1 type UTI #1 type Bloodstream Bloodstream PNA #1 cause of death PNA #1 cause of death Surgical Site Surgical Site # 1 Prevention: Hand hygiene # 1 Prevention: Hand hygiene

IV Central Line Infections Tunnel infection (2 cm or more proximal to the catheter’s exit) - Pull line Tunnel infection (2 cm or more proximal to the catheter’s exit) - Pull line Exit site infection Exit site infection #1 cause= Staph (aureus or coagulase -) #1 cause= Staph (aureus or coagulase -) Treatment: Treatment: Vanco/Gent initially Vanco/Gent initially 2 week duration without IE 2 week duration without IE With S. aureus bacteremia, perform TEE to determine length of therapy With S. aureus bacteremia, perform TEE to determine length of therapy

IV Central Line Infections Remove catheter: Remove catheter: Tunnel ID or septic thrombophlebitis Tunnel ID or septic thrombophlebitis Fungemia Fungemia Failure to clear bacteremia on ABX Failure to clear bacteremia on ABX MRSA, VRE MRSA, VRE Others- Stenotrophomonas, Pseudomonas, Corynebact JK, Bacillus, Lactobacillus Others- Stenotrophomonas, Pseudomonas, Corynebact JK, Bacillus, Lactobacillus

IV Central Line Infections Prevention: #1 is meticulous care in placing the line. Prevention: #1 is meticulous care in placing the line. Candidemia with C. albicans: Candidemia with C. albicans: Pull line Pull line fluconazole=Ampho in non-neutropenics fluconazole=Ampho in non-neutropenics Caspofungin can also be utilized Caspofungin can also be utilized

UTI Organism: #1 E. coli; S. saprophyticus Organism: #1 E. coli; S. saprophyticus Dx: No need for urine culture in most cases Dx: No need for urine culture in most cases WBCs: >10 (3-5) cfu/ml WBCs: >10 (3-5) cfu/ml Tx: Uncomplicated: 3 days of TMP-SMX or FQ (use FQ if local septra resistance rate >15-20%) Tx: Uncomplicated: 3 days of TMP-SMX or FQ (use FQ if local septra resistance rate >15-20%) Pyelonephritis: extend course to 14 days Pyelonephritis: extend course to 14 days Avoid septra, use FQ (not moxifloxacin though) Avoid septra, use FQ (not moxifloxacin though) CT scan if fever >72 hours or sepsis CT scan if fever >72 hours or sepsis

UTI Recurrent disease>3 UTIs/yr: Recurrent disease>3 UTIs/yr: Daily low dose abx (septra, macrobid) Daily low dose abx (septra, macrobid) Post-coital prophylaxis Post-coital prophylaxis Self-directed treatment Self-directed treatment Topical estrogens reduce UTI risk Topical estrogens reduce UTI risk

Prostatitis Most common = GNR’s in older men Most common = GNR’s in older men Think of GC, Chlamydia as cause in sexually active men Think of GC, Chlamydia as cause in sexually active men Avoid prostatic massage with acute infection which can lead to bacteremia Avoid prostatic massage with acute infection which can lead to bacteremia Tx: FQ for 4 wks; chronic=8 wks Tx: FQ for 4 wks; chronic=8 wks

STDs Partner networks Partner networks Recognize FQ-resistant gonococcus: Recognize FQ-resistant gonococcus: Treat with ceftriaxone or cefixime Treat with ceftriaxone or cefixime Patients with GC also treated for Chlamydia Patients with GC also treated for Chlamydia Azithromycin Azithromycin Screen for other STDs: HIV, RPR, Hep B, etc. Screen for other STDs: HIV, RPR, Hep B, etc. Lymphogranuloma venereum Lymphogranuloma venereum Small ulcer followed by bubo formation Small ulcer followed by bubo formation

Syphilis Increasing rates - MSM in California Increasing rates - MSM in California Tx: Tx: Early (<1 yr): PCN 2.4 mU x 1 Early (<1 yr): PCN 2.4 mU x 1 Late latent: PCN 2.4 mU x 3 shots Late latent: PCN 2.4 mU x 3 shots Neurosyphilis: PCN 4 mU iv q4 x 14 days Neurosyphilis: PCN 4 mU iv q4 x 14 days Desensitize in pregnancy Desensitize in pregnancy Alternates: ceftriaxone or doxycycline Alternates: ceftriaxone or doxycycline Painless ulcer of primary syphilis Secondary syphilis

FUO Definition: Continuous fever for 3 or more weeks of >38.0C despite a work-up of 3 outpatient visits or 3 hospital days Definition: Continuous fever for 3 or more weeks of >38.0C despite a work-up of 3 outpatient visits or 3 hospital days Causes: CA 33%, CVD 25%, ID 20%, Misc 13%, no diagnosis 8% Causes: CA 33%, CVD 25%, ID 20%, Misc 13%, no diagnosis 8% Workup: #1 is history, then physical and baseline labs Workup: #1 is history, then physical and baseline labs Further tests should follow positive findings Further tests should follow positive findings

Meningitis Bacterial: Bacterial: S. pneumoniae #1 (risks include CSF leak, OM/sinusitis, IE); incidence decreased with vaccination in children S. pneumoniae #1 (risks include CSF leak, OM/sinusitis, IE); incidence decreased with vaccination in children N. meningitidis: #2; petechial rash; must isolate and treat contacts. Terminal complement (c5-9) or properdin deficiencies N. meningitidis: #2; petechial rash; must isolate and treat contacts. Terminal complement (c5-9) or properdin deficiencies Vaccine among high-risk groups Vaccine among high-risk groups Travel to Mecca, Africa Dec-June Travel to Mecca, Africa Dec-June College students College students Asplenia Asplenia Military personnel in barracks Military personnel in barracks Rec: routine for 11-12 yrs; catch-up at HS/college Rec: routine for 11-12 yrs; catch-up at HS/college

Meningitis Bacterial: Bacterial: H. flu – rare during the era of vaccination H. flu – rare during the era of vaccination Listeria: GPR; Mexican style cheese, cole slaw, deli meats Listeria: GPR; Mexican style cheese, cole slaw, deli meats Risks: pregnancy/T-cell deficits/ alcoholism/ extremes of age (>50 years or 50 years or <4 weeks) Group B Strep: neonates, diabetes, etc. Group B Strep: neonates, diabetes, etc.

Meningitis Bacterial cont: Bacterial cont: Neurosurgical procedure: staph, GNRs Neurosurgical procedure: staph, GNRs Shunts: #1=Staph epi Shunts: #1=Staph epi Viral: Viral: Enterovirus (summer/fall) Enterovirus (summer/fall) HSV with seizures or MS changes HSV with seizures or MS changes WNV with flaccid paralysis, tremors WNV with flaccid paralysis, tremors Other Other

Meningitis Diagnosis: Diagnosis: LP LP CT before LP only if new-onset seizure, history of CNS disease, focal neurologic deficits, altered MS, or immunocompromised CT before LP only if new-onset seizure, history of CNS disease, focal neurologic deficits, altered MS, or immunocompromised Blood cultures, begin ABX, perform CT and then LP if safe Blood cultures, begin ABX, perform CT and then LP if safe

Meningitis Empiric tx: Empiric tx: Vanco + Ceftriaxone Vanco + Ceftriaxone Add Ampicillin: Add Ampicillin: Risk factors for Listeria or GPR on CSF gram stain Risk factors for Listeria or GPR on CSF gram stain For PCN-allergic, alternative is Septra IV For PCN-allergic, alternative is Septra IV Steroids: Give dose 15-20 min before or with ABX Steroids: Give dose 15-20 min before or with ABX Useful with H. flu in children and S. pneumoniae in all ages; also consider with obtunded patients/increased ICP Useful with H. flu in children and S. pneumoniae in all ages; also consider with obtunded patients/increased ICP Dexamethasone 0.4mg/kg q12 x 2 days Dexamethasone 0.4mg/kg q12 x 2 days Neurosurgery/trauma/shunt infection Neurosurgery/trauma/shunt infection Vanco + cefepime or meropenum Vanco + cefepime or meropenum

Meningitis Targeted Treatment S. pneumoniae Vanco + ceftriaxone Sensitive to PCN: PCN Sensitive to PCN: PCN MIC 0.1-1.0: ceftriaxone MIC 0.1-1.0: ceftriaxone MIC>1: vanco + ceftriaxone MIC>1: vanco + ceftriaxone NeisseriaCeftriaxone Listeria Ampicillin (Allergic – give septra) GBSAmpicillin H. flu Cetriaxone β-lactamase negative: ampicillin β-lactamase negative: ampicillin

CNS Focal Infection Abscess, Epidural, Subdural Abscess, Epidural, Subdural Most commonly from contiguous spread Most commonly from contiguous spread Best radiologic test: MRI Best radiologic test: MRI Surgery or aspiration for bacterial diagnosis Surgery or aspiration for bacterial diagnosis Surgery indicated with large brain abscess, subdural or epidural with neurologic compromise Surgery indicated with large brain abscess, subdural or epidural with neurologic compromise ABX: Vanco + cefepime or meropenem ABX: Vanco + cefepime or meropenem

Bartonella B. henselae: Cat scratch disease B. henselae: Cat scratch disease Young cats - bite or scratch Young cats - bite or scratch Papule at site followed by proximal LN’s Papule at site followed by proximal LN’s Neuroretinitis Neuroretinitis Diagnosis: Exam and IFA; +Warthin-starry stain of nodes Diagnosis: Exam and IFA; +Warthin-starry stain of nodes Treatment: controversial; Azithromycin may speed resolution; self resolves in 2-3mos without therapy Treatment: controversial; Azithromycin may speed resolution; self resolves in 2-3mos without therapy

Bartonella B. henselae & B. quintana: B. henselae & B. quintana: Endocarditis and bacteremia - HIV/homeless Endocarditis and bacteremia - HIV/homeless Bacillary angiomatosis in HIV Bacillary angiomatosis in HIV Vascular lesions of skin (DD KS with skin biopsy) Vascular lesions of skin (DD KS with skin biopsy) Peliosis hepatis in HIV Peliosis hepatis in HIV Blood filled cysts in the liver Blood filled cysts in the liver Treat with Doxycycline; Ceftriaxone & Gent for IE Treat with Doxycycline; Ceftriaxone & Gent for IE

Bacillary angiomatosis in HIV

Diarrhea Campylobacter: #1 in US, chicken, post-ID IBS 15% Campylobacter: #1 in US, chicken, post-ID IBS 15% Shigella : Reiter’s syndrome Shigella : Reiter’s syndrome Amebiasis: r/o Liver abscess Amebiasis: r/o Liver abscess Salmonella: typhoid fever; osteo with sickle cell disease; infects atheromas in elderly Salmonella: typhoid fever; osteo with sickle cell disease; infects atheromas in elderly Cholera: rice water stools Cholera: rice water stools Cyclospora: raspberries Cyclospora: raspberries Cryptosporidium: waterborne outbreaks Cryptosporidium: waterborne outbreaks Drinking river water in the Rockies: Giardia Drinking river water in the Rockies: Giardia >1 week: Giardia, cryptosporidium, cyclospora, isospora, and microsporidium >1 week: Giardia, cryptosporidium, cyclospora, isospora, and microsporidium #1 cause travelers: ETEC #1 cause travelers: ETEC

Clostridium difficile Antibiotic predisposition (esp. ampicillin, clindamycin, FQ) Antibiotic predisposition (esp. ampicillin, clindamycin, FQ) No longer always present; now cases seen in the community No longer always present; now cases seen in the community Use soap and water (rather than alcohol based soaps) Use soap and water (rather than alcohol based soaps) Diagnosis with C. diff stool toxin (collect 3) Diagnosis with C. diff stool toxin (collect 3) Flex sig with pseudomembranes Flex sig with pseudomembranes Isolation Isolation Treatment: Treatment: Oral flagyl Oral flagyl For severe cases with high WBC: oral vancomycin For severe cases with high WBC: oral vancomycin IV or oral flagyl is effective, but IV vancomycin is not; can use intracolonic vanco infusion (esp. with an ileus) IV or oral flagyl is effective, but IV vancomycin is not; can use intracolonic vanco infusion (esp. with an ileus) Newer agents needed Newer agents needed

E. coli 0157:H7 Notoriously associated with undercooked hamburgers Notoriously associated with undercooked hamburgers Incubation of 6 +/- 2 days Incubation of 6 +/- 2 days Bloody stools (Hemorrhagic colitis) Bloody stools (Hemorrhagic colitis) Afebrile Afebrile HUS with renal failure (begins 1 week after diarrhea in approx 5-8%) HUS with renal failure (begins 1 week after diarrhea in approx 5-8%) FQ’s may(?) increase toxin synthesis - Avoid FQ’s may(?) increase toxin synthesis - Avoid Fatalities especially at the extremes of age and with immunocompromised Fatalities especially at the extremes of age and with immunocompromised

Miscellaneous Antibiotic Data Resistance Resistance ESBL: use carbapenem ESBL: use carbapenem AmpC (SPICE): carbapenem or cefepime AmpC (SPICE): carbapenem or cefepime S. aureus sensitive to clinda but resistant to Emcin- avoid clinda use without D-test. S. aureus sensitive to clinda but resistant to Emcin- avoid clinda use without D-test. VRE: linezolid, synercid (not faecalis), daptomycin VRE: linezolid, synercid (not faecalis), daptomycin VISA: thickened cell wall VISA: thickened cell wall VRSA: VanA from enterococcus VRSA: VanA from enterococcus Strep pneumoniae: B-lactam and macrolide resistance noted Strep pneumoniae: B-lactam and macrolide resistance noted Hx of FQ use, don’t use Hx of FQ use, don’t use Tigecylcine: no Pseudomonas activity Tigecylcine: no Pseudomonas activity Ertapenem: Not for Pseudomonas or Acinetobacter Ertapenem: Not for Pseudomonas or Acinetobacter

Antibiotic Side Effects Linezolid Linezolid Low plts, serotonin syndrome Low plts, serotonin syndrome Imipenem Imipenem Seizures (meropenem has less risk) Seizures (meropenem has less risk) Synercid Synercid Nausea, must have central line Nausea, must have central line Daptomycin Daptomycin Avoid for MRSA pneumonia (use linezolid) Avoid for MRSA pneumonia (use linezolid) Telithromycin Telithromycin Liver toxicity, not in MG, QT prolongation Liver toxicity, not in MG, QT prolongation PCN allergy PCN allergy Aztreonam is OK Aztreonam is OK

Fungal Infections

Candida Never ignore Candida in the blood; always requires therapy Never ignore Candida in the blood; always requires therapy Risks: TPN, lines, GI surgery, ABX therapy, ICU stay, burns Risks: TPN, lines, GI surgery, ABX therapy, ICU stay, burns Remove central lines Remove central lines Tx with Ampho or fluconazole Tx with Ampho or fluconazole Fluconazole-resistant: C. krusei/glabrata Fluconazole-resistant: C. krusei/glabrata Caspofungin is effective Caspofungin is effective

Candida

Candida R/o systemic disease: ophtho exam, blood cultures R/o systemic disease: ophtho exam, blood cultures Complications Complications Thrombophlebitis-peripheral or central Thrombophlebitis-peripheral or central Remove lines; peripheral requires vein resection Remove lines; peripheral requires vein resection Hepatosplenic candidiasis: Hepatosplenic candidiasis: In neutropenic patients see with ANC recovery In neutropenic patients see with ANC recovery

Candiduria Rarely requires therapy; changing foley may clear funguria. Rarely requires therapy; changing foley may clear funguria. Treat in neutropenics, pregnant woman, renal transplant patients Treat in neutropenics, pregnant woman, renal transplant patients Typically treated with fluconazole Typically treated with fluconazole

Cryptococcus Pigeon droppings Pigeon droppings Most do not recall an exposure Most do not recall an exposure Immunocompetent: Immunocompetent: Fever/mild respiratory syndrome Fever/mild respiratory syndrome T-cell deficiencies (HIV, steroids, CA): T-cell deficiencies (HIV, steroids, CA): Meningitis Meningitis

Cryptococcus- Meningitis Diagnosis: Diagnosis: CSF india ink (“halo”) or CRAG CSF india ink (“halo”) or CRAG Treatment: Treatment: Pulmonary: fluconazole or none Pulmonary: fluconazole or none CNS: Ampho and 5FC x 2 wks, then fluconazole 400mg qd x 8 wks CNS: Ampho and 5FC x 2 wks, then fluconazole 400mg qd x 8 wks Check CSF OP: repeat LP or drain if elevated. Avoid steroids. May require a drain or shunt. Check CSF OP: repeat LP or drain if elevated. Avoid steroids. May require a drain or shunt. Chronic suppression in immunocompromised Chronic suppression in immunocompromised Fluconazole 200mg qd Fluconazole 200mg qd No primary prophylactic therapy recommended in HIV patients No primary prophylactic therapy recommended in HIV patients

Cryptococcus

Histoplasma Mississippi & Ohio River Valleys Mississippi & Ohio River Valleys Interstitial PNA, palate ulcers, splenomegaly, BM infiltration, meningitis Interstitial PNA, palate ulcers, splenomegaly, BM infiltration, meningitis Dx: Urine, serum, CSF antigen Dx: Urine, serum, CSF antigen Tx: Tx: Itraconazole for moderate disease Itraconazole for moderate disease Ampho for severe disease Ampho for severe disease

Histoplasma

Coccidioides immitis Southwest US “Valley Fever” Southwest US “Valley Fever” Cases in returning travelers from Mexico/SA Cases in returning travelers from Mexico/SA Sxs: Sxs: Most often asymptomatic or ‘flu-like’ Most often asymptomatic or ‘flu-like’ Arthralgia, EN, fever, pulmonary infiltrate - “Desert Rheumatism” Arthralgia, EN, fever, pulmonary infiltrate - “Desert Rheumatism” Dissemination: HIV, pregnancy (3rd trimester), Filipinos, blacks, cellular immunodeficiency Dissemination: HIV, pregnancy (3rd trimester), Filipinos, blacks, cellular immunodeficiency Skin, CNS (meningitis), arthritis, osteomyelitis Skin, CNS (meningitis), arthritis, osteomyelitis

Coccidioides immitis Diagnosis: Diagnosis: CF of serum or CSF CF of serum or CSF Culture plates - notify the lab as hazardous Culture plates - notify the lab as hazardous Treatment Treatment Mild: Most resolved without therapy; however most would treat with Itra or Fluc for 6+ wks Mild: Most resolved without therapy; however most would treat with Itra or Fluc for 6+ wks Locally severe or disseminated: Ampho B Locally severe or disseminated: Ampho B Itraconazole>fluconazole for bony disease Itraconazole>fluconazole for bony disease Voriconazole or Posaconazole alternative agents Voriconazole or Posaconazole alternative agents Follow clinically and with CF titers Follow clinically and with CF titers

Sporotrichosis Gardeners/ thorn exposure Gardeners/ thorn exposure Local nodule and proximal adenopathy Local nodule and proximal adenopathy Complications include osteomyelitis and dissemination with pulm or CNS disease Complications include osteomyelitis and dissemination with pulm or CNS disease Tx: Itraconazole (CNS use Amphotericin) Tx: Itraconazole (CNS use Amphotericin)

Sporothrix

Aspergillus ABPA: Steroids, itraconazole ABPA: Steroids, itraconazole Aspergilloma: Surgery for hemoptysis; consider itraconazole Aspergilloma: Surgery for hemoptysis; consider itraconazole Invasive Aspergillosis: Pulmonary #1 location Invasive Aspergillosis: Pulmonary #1 location Hemoptysis due to infarction Hemoptysis due to infarction High resolution CT: halo sign, crescent sign, cavitation High resolution CT: halo sign, crescent sign, cavitation Voriconazole > Amphotericin b Voriconazole > Amphotericin b Caspofungin can be used for refractory disease Caspofungin can be used for refractory disease Risk for Mucor or Rhizopus with non-Ampho regimens Risk for Mucor or Rhizopus with non-Ampho regimens

Aspergillus

Mucormycosis Diabetics Diabetics esp with ketoacidosis and poor glucose control esp with ketoacidosis and poor glucose control Sinus disease with extension into CNS Sinus disease with extension into CNS Black eschar on nasal mucosa Black eschar on nasal mucosa **Immunocompromised: Pulm with infarcts/ cavities **Immunocompromised: Pulm with infarcts/ cavities Dx with biopsy Dx with biopsy Tx: Immediate debridement and Amphotericin Tx: Immediate debridement and Amphotericin Posaconazole very effective Posaconazole very effective

Antifungal Agents Fluconazole: Fluconazole: Candida, Crypto, Cocci Candida, Crypto, Cocci High doses: chapped skin High doses: chapped skin Itraconazole: Itraconazole: Histo, blasto, sporotrichosis, aspergillus, and cocci (bony disease) Histo, blasto, sporotrichosis, aspergillus, and cocci (bony disease) Issue: poor absorption; check levels Issue: poor absorption; check levels Voriconazole: Voriconazole: Aspergillus, Fusarium/Scedosorium; also for candida, cocci, etc. Aspergillus, Fusarium/Scedosorium; also for candida, cocci, etc. Side effect: visual effects in up to 30% Side effect: visual effects in up to 30% Caspofungin: Caspofungin: Candida, aspergillus (Refractory disease) Candida, aspergillus (Refractory disease) NOT cryptococcus or zygomyces NOT cryptococcus or zygomyces

Cellular Defects BMT: BMT: 1st Month: bacterial due to surgery/nosocomial 1st Month: bacterial due to surgery/nosocomial donor organ infection; HSV reactivation donor organ infection; HSV reactivation 1-6 Months: CMV, EBV, VZV, HHV6, Aspergillus, PCP, TB, nematodes 1-6 Months: CMV, EBV, VZV, HHV6, Aspergillus, PCP, TB, nematodes 4 months : Cryptococcus 4 months : Cryptococcus >6 months: Community acquired infections >6 months: Community acquired infections CMV is the most important infection in sero-neg patients, use sero-neg donor and neg blood products; presents as malaise, fever, PNA, diarrhea CMV is the most important infection in sero-neg patients, use sero-neg donor and neg blood products; presents as malaise, fever, PNA, diarrhea

Viral Infections: Post Transplant HHV6 HHV6 Hepatitis, PNA, encephalitis Hepatitis, PNA, encephalitis HHV8 HHV8 Castlemans Castlemans KS KS PEL PEL JC JC PML PML BK BK Renal transplant: nephropathy (“decoy cells”) Renal transplant: nephropathy (“decoy cells”) Stem cell: hemorrhagic cystitis (also due to adenovirus) Stem cell: hemorrhagic cystitis (also due to adenovirus)

Asplenia Encapsulated organisms : H. flu, S. pneumoniae, Neisseria Encapsulated organisms : H. flu, S. pneumoniae, Neisseria Vaccinate 2+ wks before splenectomy Vaccinate 2+ wks before splenectomy Babesiosis Babesiosis Malaria Malaria Captonocytophaga Captonocytophaga

Humoral Defects IgA deficiency: IgA deficiency: Most common primary immune defect. Most common primary immune defect. Atopic, Giardia, potential for mucosal infections Atopic, Giardia, potential for mucosal infections Hypogammaglobulinemia: Low IgG (CVID) Hypogammaglobulinemia: Low IgG (CVID) Sinopulmonary infections, Echovirus Sinopulmonary infections, Echovirus Dx: Quantitative Ig levels; Ig levels after vaccination Dx: Quantitative Ig levels; Ig levels after vaccination If total IgG normal and clinical setting appropriate, check IgG subclasses If total IgG normal and clinical setting appropriate, check IgG subclasses Tx: Ig replacement only if recurrent infections Tx: Ig replacement only if recurrent infections

Complement Deficiencies Early (C1,2,4): Early (C1,2,4): Sinopulmonary ID’s Sinopulmonary ID’s CVD (esp SLE with C2 deficiency) CVD (esp SLE with C2 deficiency) Late (C5-9) Late (C5-9) Meningococcemia - recurrent Meningococcemia - recurrent Check CH50 assay (if normal, consider C9, factor D, properdin) Check CH50 assay (if normal, consider C9, factor D, properdin)

Chronic granulomatous disease NADPH oxidase defect NADPH oxidase defect Catalase-positive infections: Staph, Burkholderia, aspergillus Catalase-positive infections: Staph, Burkholderia, aspergillus Liver abscesses Liver abscesses Dx: Nitroblue tetrazolium test Dx: Nitroblue tetrazolium test Tx: Septra and interferon to reduce number of infections Tx: Septra and interferon to reduce number of infections

Diabetes UTI/pyelonephritis (E. coli #1) UTI/pyelonephritis (E. coli #1) FQ or AMP/GENT FQ or AMP/GENT Candida mucosal infections Candida mucosal infections Topical antifungal or single dose fluconazole Topical antifungal or single dose fluconazole Rhinocerebral mucormycosis Rhinocerebral mucormycosis Malignant External Otitis: Pseudomonas Malignant External Otitis: Pseudomonas Surgical debridement, Imipenem or ceftaz or cipro (use agent against Pseudomonas) Surgical debridement, Imipenem or ceftaz or cipro (use agent against Pseudomonas) Diabetic foot infections Diabetic foot infections Cipro/Clinda or Zosyn; r/o osteomyelitis Cipro/Clinda or Zosyn; r/o osteomyelitis

Prion Disease PrP SC PrP SC Altered 3-dimensional structure Altered 3-dimensional structure Types: Types: Sporadic #1 Sporadic #1 Genetic #2 Genetic #2 Acquired/Variant #3 Acquired/Variant #3 Kuru: New Guinea Kuru: New Guinea

Prion Disease Sporadic Sporadic 60 years of age 60 years of age Rapidly fatal (8 months) Rapidly fatal (8 months) Dementia, change personality, visual, gait problems Dementia, change personality, visual, gait problems Death due to aspiration PNA Death due to aspiration PNA Genetic Genetic 40 years of age 40 years of age Slower disease course Slower disease course Parkinsonism, ataxia initially Parkinsonism, ataxia initially

Prion Disease Acquired Acquired Iatrogenic Iatrogenic GH, dura mater grafts, corneal transplant, EEG electrodes GH, dura mater grafts, corneal transplant, EEG electrodes Sterilize with very high temperatures Sterilize with very high temperatures 15 month life expectancy 15 month life expectancy Variant CJD “mad cow” Variant CJD “mad cow” Eating meat from U.K. Eating meat from U.K. Age 28 years Age 28 years Psychiatric symptoms initially, painful body areas Psychiatric symptoms initially, painful body areas

Prion Disease Diagnosis Definitive Diagnosis: Brain biopsy Definitive Diagnosis: Brain biopsy Tonsil biopsy only for variant CJD Tonsil biopsy only for variant CJD EEG: sharp or triphasic wave q 1 second EEG: sharp or triphasic wave q 1 second Sporadic, not variant Sporadic, not variant CSF: 14-3-3 protein CSF: 14-3-3 protein MRI MRI DWI: hyperintensity in basal ganglia/cortical gyri DWI: hyperintensity in basal ganglia/cortical gyri Pulvinar sign: posterior>anterior thalmus brightness Pulvinar sign: posterior>anterior thalmus brightness Only in Variant CJD Only in Variant CJD Treatment: None; always fatal Treatment: None; always fatal

HIV 33 million cases : Africa has highest number 33 million cases : Africa has highest number #1 transmission route: Heterosexual activity #1 transmission route: Heterosexual activity U.S. U.S. Stable number of new infections per year (60,000) Stable number of new infections per year (60,000) Increasing rate in women Increasing rate in women Hispanics and African Americans Hispanics and African Americans 67% of the new infections 67% of the new infections False sense of security False sense of security

Natural History of HIV Viral transmission Viral transmission Acute retroviral syndrome Acute retroviral syndrome Clinical recovery & seroconversion Clinical recovery & seroconversion Asymptomatic chronic HIV infection - 8 yrs* Asymptomatic chronic HIV infection - 8 yrs* Symptomatic infection - 1.3 yrs* Symptomatic infection - 1.3 yrs* Death Death *Without HAART

Clinical Manifestations Acute Retroviral Syndrome Occurs 2-4 weeks after exposure Occurs 2-4 weeks after exposure Broad Tropism of HIV Broad Tropism of HIV Symptoms: Symptoms: Fever-Myalgias Fever-Myalgias Adenopathy-HSM Adenopathy-HSM Pharyngitis-Weight Loss Pharyngitis-Weight Loss Rash/Mucosal lesions-Thrush Rash/Mucosal lesions-Thrush GI symptoms-Neurologic GI symptoms-Neurologic

Diagnosis During the Acute Infection High index of suspicion High index of suspicion Viral load PCR Viral load PCR p24 Antigen is positive 3-5 days later than the VL p24 Antigen is positive 3-5 days later than the VL Basic Labs: Basic Labs: Transaminitis, lymphopenia, thrombocytopenia Transaminitis, lymphopenia, thrombocytopenia ELISA testing may take 3 weeks - 6 months ELISA testing may take 3 weeks - 6 months Cannot rely on ELISA testing in acute phase Cannot rely on ELISA testing in acute phase No utility of a CD4 count for the diagnosis No utility of a CD4 count for the diagnosis

HIV Related Complications <200/mm3 <200/mm3 PCP, disseminated histoplasmosis or coccidioidomycosis, extrapulmonary TB, PML, wasting syndrome, peripheral neuropathy, HIV-associated dementia, cardiomyopathy PCP, disseminated histoplasmosis or coccidioidomycosis, extrapulmonary TB, PML, wasting syndrome, peripheral neuropathy, HIV-associated dementia, cardiomyopathy <100/mm3 <100/mm3 Disseminated herpes simplex, toxoplasmosis, cryptococcosis, microsporidiosis, Candida esophagitis Disseminated herpes simplex, toxoplasmosis, cryptococcosis, microsporidiosis, Candida esophagitis <50/mm3 <50/mm3 CMV, MAC, CNS lymphoma (EBV) CMV, MAC, CNS lymphoma (EBV)

Oral Leukoplakia: EBV

Oral KS

Diagnosis of Chronic HIV Infection ELISA ELISA Highest sensitivity and specificity Highest sensitivity and specificity False negative ELISA: False negative ELISA: ‘window period,’ agammaglobulinemia, technical errors, atypical host response ‘window period,’ agammaglobulinemia, technical errors, atypical host response False-positive ELISA: False-positive ELISA: autoantibodies (Lupus, transfusions, multiple pregnancies), immunizations, or technical error autoantibodies (Lupus, transfusions, multiple pregnancies), immunizations, or technical error Rapid tests are as sens/spec as blood tests (20 minutes) Rapid tests are as sens/spec as blood tests (20 minutes) Confirm with WB Confirm with WB Follow CD4 and viral loads for clinical status Follow CD4 and viral loads for clinical status Resistance testing: indicated for acute and chronic infection before starting HAART and again at treatment failure Resistance testing: indicated for acute and chronic infection before starting HAART and again at treatment failure

Immune Reconstitution Syndrome Infections are quiescent and become clinically apparent with immune restoration Infections are quiescent and become clinically apparent with immune restoration Most common with Most common with Initial CD4<50/mm 3 Initial CD4<50/mm 3 Dramatic response to ART with a rapid decline in VL Dramatic response to ART with a rapid decline in VL Treat with continued HAART and therapy against OI; consider steroids with severe symptoms Treat with continued HAART and therapy against OI; consider steroids with severe symptoms

Immune Reconstitution Syndrome InfectionClinical Feature InfectionClinical Feature MACFocal adenitis MACFocal adenitis CMVVitritis CMVVitritis TBPneumonitis, LN TBPneumonitis, LN CryptococcusMeningitis CryptococcusMeningitis Hepatitis CHepatitis Hepatitis CHepatitis

Treatment Options in the Management of HIV

Initiating Treatment of HIV Initiating Treatment of HIV Recommendations: Recommendations: Symptomatic HIV disease Symptomatic HIV disease OI or chronic weight loss OI or chronic weight loss AID’s AID’s CD4<350 CD4<350 Pregnancy Pregnancy

2007 DHHS/USPHS Guidelines Plasma HIV Clinical Category CD4RNARecommendation Symptomatic (AIDS, severe symptoms)Any AnyTreat Asymptomatic >200/mm 3 & AnyOffer treatment, but  350/mm 3 controversy exists (18-19%); most treat Asymptomatic >350 Asymptomatic >350 Asymptomatic<200/mm 3 AnyTreat (  14%) Defer (follow closely) ≥100,000 Defer therapy <100,000

Initial Regimen 2 NRTI’s and PI 2 NRTI’s and PI 2 NRTI’s and 2 PI’s 2 NRTI’s and 2 PI’s 2 NRTI’s and NNRTI 2 NRTI’s and NNRTI Tenofovir/FTC (Truvada) Plus Kaletra, fosamprenavir, darunavir or Sustiva Use TDF/FTC if patient has concurrent hepatitis B

Nucleoside Reverse Transcriptase Inhibitors Zidovudine (AZT): avoid concurrent D4T Zidovudine (AZT): avoid concurrent D4T Didanosine (DDI) Didanosine (DDI) Zalcitabine (DDC): avoid DDI or D4T Zalcitabine (DDC): avoid DDI or D4T Stavudine (D4T) Stavudine (D4T) Lamivudine (3TC) Lamivudine (3TC) Emtricitabine (FTC) Emtricitabine (FTC) Abacavir: (with AZT and 3TC=Trizivir) Abacavir: (with AZT and 3TC=Trizivir) Tenofovir: Newest NRTI Tenofovir: Newest NRTI

Non-Nucleoside Reverse Transcriptase Inhibitors Nevirapine Nevirapine Efavirenz Efavirenz Delavirdine – no longer utilized Delavirdine – no longer utilized Etravirine (TMC125) Etravirine (TMC125)

Protease-Inhibitors Indinavir Indinavir Saquinavir: use soft gel Saquinavir: use soft gel Ritonavir: use in combination Ritonavir: use in combination Nelfinavir Nelfinavir Amprenavir & Fosamprenavir Amprenavir & Fosamprenavir Lopinavir/Ritonavir (Kaletra) Lopinavir/Ritonavir (Kaletra) Atazanavir Atazanavir Tipranavir Tipranavir Darunavir Darunavir

Adverse Events - NTRI’s Lactic acidosis-hepatic steatosis Lactic acidosis-hepatic steatosis D4T, DDI, DDC, AZT are most common D4T, DDI, DDC, AZT are most common Tenofovir and abacavir the safest in terms of lactic acidosis Tenofovir and abacavir the safest in terms of lactic acidosis Elevated lactic acid, low HCO3, AG 20+, and elevated LFT’s due mitochondrial injury Elevated lactic acid, low HCO3, AG 20+, and elevated LFT’s due mitochondrial injury Therapy: d/c meds, supportive care and riboflavin, Therapy: d/c meds, supportive care and riboflavin, ? Carnitine, thiamine

Adverse Events - NTRI’s Abacavir – check HLA 5701 Abacavir – check HLA 5701 Hypersensitivity reaction with fever, rash, GI, lethargy, low BP and elevated LFT’s / CK Hypersensitivity reaction with fever, rash, GI, lethargy, low BP and elevated LFT’s / CK Occurs in the first 6 weeks of therapy Occurs in the first 6 weeks of therapy Drug should be discontinued and never restarted Drug should be discontinued and never restarted DDI, D4T, DDC DDI, D4T, DDC Peripheral neuropathy Peripheral neuropathy DDI/hydroxyurea DDI/hydroxyurea Pancreatitis Pancreatitis D4T D4T lipoatrophy lipoatrophy

Adverse Events - NNTRI’s: Efavirenz Efavirenz CNS side effects and rash CNS side effects and rash Cannot use in pregnancy Cannot use in pregnancy Nevirapine Nevirapine Severe rash, SJS, transaminitis/liver failure Severe rash, SJS, transaminitis/liver failure Begin at low dose (1 tablet) for the first 2 weeks Begin at low dose (1 tablet) for the first 2 weeks

Adverse Events - Protease Inhibitors Lipodystrophy Lipodystrophy Correlates with the time on PI’s & duration of HIV Correlates with the time on PI’s & duration of HIV Diabetes Diabetes Hyperlipidemia Hyperlipidemia Due to both HIV and PI’s (not atazanavir) Due to both HIV and PI’s (not atazanavir) Osteopenia Osteopenia CV Events CV Events

Adverse Events - Protease Inhibitors Indinavir Indinavir Nephrolithiasis, indirect bilirubinemia, paronychia, and alopecia Nephrolithiasis, indirect bilirubinemia, paronychia, and alopecia Nelfinavir Nelfinavir Diarrhea Diarrhea Lopinavir/Ritonavir Lopinavir/Ritonavir GI upset, diarrhea GI upset, diarrhea Atazanavir Atazanavir High bilirubin level High bilirubin level **Lots of drug-drug interactions **Lots of drug-drug interactions

Reasons for Changing Therapy Drug failure by CD4, VL or symptoms Drug failure by CD4, VL or symptoms Goal is VL <50 copies/ml Goal is VL <50 copies/ml Assure compliance Assure compliance Adverse effects Adverse effects Regimen inconvenience Regimen inconvenience

Changing Therapy For an adverse event For an adverse event May switch medication for a new one if causative drug is known May switch medication for a new one if causative drug is known For drug failure For drug failure Drug resistance testing – genotype (VL must be >1000) Drug resistance testing – genotype (VL must be >1000) Change to an ‘all new regimen’ Change to an ‘all new regimen’ Do not simply add or change a single agent to a failing regimen Do not simply add or change a single agent to a failing regimen Lowest barrier for resistance is NNRTI’s – single point mutation (K103) confers class resistance Lowest barrier for resistance is NNRTI’s – single point mutation (K103) confers class resistance

Prophylaxis Against Opportunistic Infections Pneumocystis carinii/jiroveci (PCP) Pneumocystis carinii/jiroveci (PCP) CD4 2 weeks, oral candidiasis CD4 2 weeks, oral candidiasis TMP-SMZ 1 DS po qd or qod TMP-SMZ 1 DS po qd or qod Dapsone 100 mg po qd Dapsone 100 mg po qd Atovaquone 1500 mg po qd Atovaquone 1500 mg po qd Aerosolized Pentamidine q month Aerosolized Pentamidine q month

Toxoplasmosis CD4<100 and +IgG serology CD4<100 and +IgG serology TMP-SMZ 1 DS po qd or qod TMP-SMZ 1 DS po qd or qod Dapsone and Pyrimethamine q week Dapsone and Pyrimethamine q week

Mycobacteria Tuberculosis-Latent Infection Tuberculosis-Latent Infection +PPD at >/=5 mm +PPD at >/=5 mm INH 300 mg qd and B6 50 mg qd x 9 mos INH 300 mg qd and B6 50 mg qd x 9 mos MAC MAC CD4<50 CD4<50 Azithromycin 1250 mg po qweek Azithromycin 1250 mg po qweek Clarithromycin 500 mg po bid Clarithromycin 500 mg po bid Rifabutin 300 mg po qd Rifabutin 300 mg po qd

Stopping OI Prophylaxis PCP primary prophylaxis with a CD4>200 and VL 200 and VL<50 for 3-6 months May use the same criteria to d/c secondary prophylaxis May use the same criteria to d/c secondary prophylaxis Stopping MAC, CMV or Cryptococcus primary prophylaxis with CD4>100, VL 100, VL<50 on HAART for 3-6 months

Vaccinations May cause transient increase in VL May cause transient increase in VL Clinically insignificant Clinically insignificant Recommended: Recommended: Pneumovax & HIB Pneumovax & HIB Influenza q year Influenza q year Hepatitis A and B Hepatitis A and B Tetanus-diphtheria Tetanus-diphtheria Contraindicated: Live vaccines such as oral polio, varicella, BCG, smallpox, yellow fever Contraindicated: Live vaccines such as oral polio, varicella, BCG, smallpox, yellow fever MMR given at high CD4 count (>200) MMR given at high CD4 count (>200)

Opportunistic Infections PCP PCP Slowly progressive SOB, cough, fevers Slowly progressive SOB, cough, fevers CXR: diffuse infiltrates, PTX, cyst (apical on Pentam) CXR: diffuse infiltrates, PTX, cyst (apical on Pentam) Labs: high LDH, hypoxia Labs: high LDH, hypoxia Dx: PCP DFA of sputum, silver stains Dx: PCP DFA of sputum, silver stains Tx: mild/mod: oral septra x 21 days Tx: mild/mod: oral septra x 21 days Tx: severe: IV septra (#1 drug of tx & proph) Tx: severe: IV septra (#1 drug of tx & proph) Steroids if paO2 35 Steroids if paO2 35

CMV #1 is retinitis #1 is retinitis Classic retinal appearance Classic retinal appearance GI - colitis, esophagitis, oral ulcers GI - colitis, esophagitis, oral ulcers CNS: CNS: #1 cause of spinal infection with radiculopathy #1 cause of spinal infection with radiculopathy Dx: eye: exam; CNS: PCR; GI or pulm by biopsy & seeing inclusions Dx: eye: exam; CNS: PCR; GI or pulm by biopsy & seeing inclusions Tx: Systemic Gancyclovir Tx: Systemic Gancyclovir

Toxo Infection seen almost solely in those who are seropositive (IgG) Infection seen almost solely in those who are seropositive (IgG) CNS disease with multiple ring enhancing lesions CNS disease with multiple ring enhancing lesions Tx: empiric pyrimethamine & sulfadiazine Tx: empiric pyrimethamine & sulfadiazine Should be clinical & radiologic response in 1-2 wks (no response - perform brain bx) Should be clinical & radiologic response in 1-2 wks (no response - perform brain bx) DD= NHL DD= NHL

CNS Lesions Toxo: Ring enhancing lesion(s) Toxo: Ring enhancing lesion(s) CMV: periventricular white matter changes CMV: periventricular white matter changes Cryptococcus: usually normal head CT; may show increase ICP Cryptococcus: usually normal head CT; may show increase ICP NHL: Lesion(s)-may confuse with toxo NHL: Lesion(s)-may confuse with toxo PML: subcortical white matter disease; due to JC virus PML: subcortical white matter disease; due to JC virus AIDS - ADC AIDS - ADC Treatment of PML & ADC is HAART! Treatment of PML & ADC is HAART!

Malignancies AIDS defining: AIDS defining: KS, invasive cervical, high/int grade NHL KS, invasive cervical, high/int grade NHL Viral Etiologies: Viral Etiologies: LymphomaEBV LymphomaEBV Cervical CancerHPV 16,18, 31,33 Cervical CancerHPV 16,18, 31,33 Anal CancerHPV Anal CancerHPV KS, PELHHV8 KS, PELHHV8

Kaposi’s Sarcoma

Prophylaxis after a Sexual of Needlestick Exposure After a ‘high-risk’ event After a ‘high-risk’ event ?blood, bore of needle, entry into vessel. ?blood, bore of needle, entry into vessel. Use 2-3 active agents Use 2-3 active agents AZT/3TC or TDF/FTC, and possibly a PI for 30 days AZT/3TC or TDF/FTC, and possibly a PI for 30 days Check ELISA’s at day 0, 1-2, and 6 months Check ELISA’s at day 0, 1-2, and 6 months VL with seroconversion-like symptoms VL with seroconversion-like symptoms Prophylaxis after sexual exposure follows similar guidelines Prophylaxis after sexual exposure follows similar guidelines Begin meds in <72 hrs Begin meds in <72 hrs

Questions

Smallpox

HSV1 Encephalitis

Shingles

Meningococcemia

Toxoplasmosis in AIDS

Neurocysticercosis

Chagas Disease

Lipodystrophy – Protease Inhibitor Use

Candida

Schistosomiasis causing liver dysfunction; egg deposit with granulomatous reaction

Plasmodium falciparum

Good Luck on THE BOARDS!

Board Review Infectious Diseases. Exposure History Southwest US: Coccidioidomycosis Southwest US: Coccidioidomycosis Midwest US: Histoplasmosis Midwest.

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Board Review Infectious Diseases. Exposure History Southwest US: Coccidioidomycosis Southwest US: Coccidioidomycosis Midwest US: Histoplasmosis Midwest.

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Presentation on theme: "Board Review Infectious Diseases. Exposure History Southwest US: Coccidioidomycosis Southwest US: Coccidioidomycosis Midwest US: Histoplasmosis Midwest."— Presentation transcript:

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