Adult Infectious Diseases Over 200 Case Studies PDF

All rights reserved. No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the publisher, except in the case of brief quotations embodied in critical reviews and certain other noncommercial uses permitted by copyright law. ISBN: 978-1-4835904-9-3 The author would like to thank his medical students and patients for the years of enjoyment of bedside, clinical medicine. Table of Contents *Questions and answers at the end of each section * Antibiotics Introduction Case 1-Aminoglycosides Bacteriostatic vs. Bacteriocidal Case 2-Antifungals Case 3-Aztreonam Case 4-Cephalosporins Case 5-Clindamycin Case 6-Coumadin and antibiotics Case 7-Daptomycin Case 8-Ext. Spect. penicillins (Zosyn/Timentin) Case 9-Linezolid Case 10-Macrolides Case 11-Metronidazole Case 12-Nucleoside inhibitors Case 13-Penam agents Case 14-Penicillin Case 15-Pregnancy Case 16-Quinolones Case 17-Rifampin Case 18-Semi-synthetic penicillins (Nafcillin) Case 19-Sulfa Case 20-Tetracycline Protein synthesis inhibitors Case 21-Vancomycin Case 22-Colistin Basic Microbiology Introduction- Basic Microbiology Gram + and Gram – Bacteria MICs Gram stain Fungi Viruses Protozoa Case 23- Gram + cocci in clusters Case 24- Gram + cocci in chains Streptococcus pneumonia Case 25- Gram + rods Case 26- Gram – diplococci Case 27- Gram – coccobacilli Case 28- Gram – rods- Tribe 1 Case 28- Gram – rods- Tribe 2 Case 29- Anaerobes above the diaphragm Case 30- Anaerobes below the diaphragm Case 31- Gram + anaerobic rods Nocardia Case 32- Rickettsiaceae Case 33- Bartonellae Case 34- Borrelia Case 35- Zoonotic bacteria Case 36- Fungi Case 37- Mycobacterium Case 38- Mycoplasma/Ureaplasma Case 39- Chlamydia Case 40- ESBLs AmpC beta-lactamases Cardiovascular Infections Case 41- Bacterial endocarditis Prophylaxis Case 42- Pericarditis Case 43- Myocarditis Case 44-Pacemaker infections Case 45- Mediastinitis Harvest site infections (post op) Case 46-Prosthetic valve endocarditis Fever of Unknown Origin Introduction- pathogenesis of fever; definitions of FUO Case 47- High Biomarkers; ESR and CRP Case 48-Fever with cancer Case 49-Fever with granulomas Case 50-Fever with collagen vascular disease Case 51- Fever with medications Case 52- Fever with endocrine problems Case 53-Fever with hematomas Case 54-Fever with myositis/rhabdomyolysis Fever associated with joint pains Case 55- Fever with dental/ENT infections Case 56-Fever with arthropod bites Case 57-Fever with international travel Case 58-Fever with abdominal pain/diarrhea Case 59-Fever with jaundice/high LFTs Case 60-Fever with hemolytic anemia Case 61-Fever in the ICU Case 62- Fever with rarer infections Work up of FUO Fungal infections Introduction-Antifungal drugs Case 63-Dermatophyte infections Case 64-Onychomycosis Case 65- Candida infections Case 66-Candidemia Case 67-Aspergillus infections Case 68- Cryptococcosis Case 69-Blastomycosis Case 70-Histoplasmosis Case 71-Coccidiomycosis Case 72-Rare Fungal infections Case 73-Fever and neutropenia Gastrointestinal infections Case 74-Intraabdominal infections Case 75-Diverticulitis Case 76-Intraabdominal abscess Case 77-H. pylori infections Case 78-Clostridia difficile infections Case 79-Gastroenteritis Case 80-Subacute Bacterial Peritonitis (SBP) Case 81-Hepatitis B Case 82-Pancreatic infections Case 83- Hepatitis C Genitourinary infections Introduction-UTI definition Case 84-Cystitis Case 85-Prostatitis/epididymitis Case 86-Pyelonephritis Case 87-Healthcare associated UTI Case 88-Dysuria syndrome Case 89- Asymptomatic UTI Case 90-Fungal UTI Case 91-PID Case 92-Prevention of UTIs Healthcare Associated infections Introductions-Types of HCAIs Case 93-Pathogens associated with HCAIs Case 94-Primary bacteremia (line related) Case 95-Healthcare associated Pneumonia Case 96-FUO in the ICU Case 97- Healthcare associated UTIs Case 98-Surgical wound infections HIV infections Case 99-Introduction/Pathogenesis HIV natural history HIV Resistance Case 100-HIV epidemiology Case 101-Cell mediated Immunity Opportunistic infections Case 102-Pneumocystis pneumonia Case 103-Confirming tests Case 104-When to treat Case 105-Picking a Rx regimen Case 106-Noncompliance and Chemoprophylaxis Immunocompromised Patients Introduction/The Adaptive Immune System Case 107-Chronic Kidney disease Case 108-Chronic Liver disease Case 109-Splenectomy patients Case 110-Fever and Neutropenia Case 111-Myasis Case 112-Transplant patients Musculoskeletal infections Case 113-Septic arthritis Differentiating Gonococcal and Non GC septic arthritis Case 114-Prosthetic septic arthritis Case 115-Vertebral osteomyelitis/discitis Case 116-Palmer space infections Case 117-Diabetic osteomyelitis Case 118-Septic bursitis Case 119-Chronic osteomyelitis Case 120-Bacterial tenosynovitis Case 121-Dental Prophylaxis forPJI Nervous System infections Case 122-Bacterial meningitis Case 123-Aseptic meningitis Case 124-Brain abscess Case 125- Epidural abscess Case 126-Encephalitis Case 127-Jakob-Creutzfeldt disease (Prion disease) Case 128-Transvere myelitis Case 129-Rabies Nuclear Medicine Testing Case 130-Gallium scan versus Indium scans Case 131-Scans for Osteomyelitis Outpatient infections Case 132-Furunculitis/Carbunculitis Case 133-Herpes Zoster Case 134-Pharnygitis/Tonsillitis Case 135-Ear infections Case 136-Sinusitis Case 137-Acute bronchitis Case 138-Chronic bronchitis Case 139-Walking pneumonia Case 140-Antibiotic prophylaxis Case 141-Leukocytosis/ High Sed Rate Case 142-Mononucleosis Case 143-Procalcitonin Levels Case 144-Rheumatic Fever Parasitic infections Case 145-155-Protozoal infections (11) Case 145-Acanthamoeba Case 146-Naeglaria Case 147-Plasmodium Case 148-Toxoplasmosis Case 149-Giardia Case 150-Entamoeba Case 151-Leishmaniasis Case 152-Trypanosomiasis Case 153-Babesiosis Case 154-Cryptosporidia Case 155-Trichomoniasis Case 156-170-Metazoal infections Case 156-164-Nematode infections (11) Case 156-Pinworm (Enterobius) Case 157-Roundworm (Ascariasis) Case 158-Hookworm (Necator) Case 159-Dog hookworm (Ancylostoma) Case 160-Strongyloides Case 161-Trichinella Case 162-Wuchereria Case 163-Onchocerciasis Loaloa Guinea worm (Dracunculus) Case 164-Baylisascaris (Raccoon ascaris) Case 165-168-Cestode infections (tapeworm) (4) Case 165-Cysticercosis (Taenia solium) Case 166-Echinococcus granulosus Case 167-Echinococcus multilocularis Case 168-Fish tapeworm (Diphyllabothrium latum) Case 169-170-Trematode infections (Flukes) (2) Case 169-Schistosomiasis Case 170-Oriental Lung Fluke (Paragonimus) Pulmonary infections Case 171-Aspiration pneumonia Case 172-Healthcare associated pneumonia Bronchoscopy Case 173-Cavitary pneumonia Case 174-Tuberculosis Case 175-Empyema Case 176-Contagious pneumonias Case 177-Local complications of pneumonia Case 178-CURB-65 Score Case 179-Lobar pneumonia Case 180-Atypical pneumonia Case 181-Whooping cough (Bordetella pertussis) Case 182-MAI/MAC Case 183-Influenza Case 184-Lung abscess Case 185-Chronic bronchiectasis Sepsis Introduction-Definitions- SIRS, Sepsis, Severe Sepsis Case 186-Septic shock Case 187-Fluid resuscitation, pressor support Case 188- Low Dose Hydrocortisone Case 189-ARDS Case 190-DIC, Activated Protein C Supportive Care Mortality Rate Procalcitonin values SOFA score Sexually Transmitted Infections Case 191-Genital ulcers Case 192-Syphilis Case 193-Gonorrhea Case 194-Nongonococcal infections (Chlamydia) Case 195-Trichomonas Case 196-Herpes Simplex 2 infections Case 197-Candida infections Case 198-Bacterial vaginosis Case 199-HPV (Condyloma acuminatum) Case 200-Scabies Pubic lice Case 201-Rape Case 202-PID Skin and Soft Tissue Infections Case 203-Pediatric exanthems Case 204-Cellulitis Case 205-Facial cellulitis Impetigo Case 206-Diabetic foot infections Wound vacuum therapy Case 207- Vein Harvest site infections, special cases Case 208-Hidradenitis suppuritiva Case 209-Necrotizing fasciitis Case 210-Bite infections- human, cat/dog Case 211-MRSA infections Case 212-Infected decubitus ulcers Case 213-Herpetic whitlow Case 214-Papulosquamous rashes Case 215-Infected venous ulcers Case 216-Gas gangrene (myonecrosis) Case 217-Cat scratch disease Lymphadenopathy/lymphadenitis Case 218-Erythema gangrenosum Case 219-Infected heel ulcer Case 220-Vibrio vulnificus Aeromonas hydrophilia Vaccines Introduction (Vaccine efficacy) Schedule for Adult vaccinations Case 221-Tetanus (Tdap), Pneumococcal. vaccines Case 222-International Travel Vaccines, meningococcal vaccines Case 223-Japanese Encephalitis Vaccine Case 224-Shingles/Chicken Pox Vaccine Case 225-Vaccines in splenectomized patients, HiB vaccine Case 226-Influenza Vaccines Hepatitis A vaccine Hepatitis B vaccine HPV vaccine 15 Principles of patient care What we can learn from Sherlock Holmes About the Author Antibiotics Introduction: The issue with antibiotics is that they are generally used for “short term” treatments in patients. Their development by pharmaceutical companies is competing against long-term diseases like diabetes, COPD, MS, asthma and heart disease where medications are used for years. Pharmaceutical companies put their financial resources more in longer term diseases (such as HIV, Hepatitis C) where the “return on investment” (ROI) is higher. The pipeline for new antimicrobials has slowed down over the last several decades. Case 1 A 20 year old female presents to the ER with acute abdominal pain and peritonitis from a ruptured appendix. You empirically place her on IV metronidazole (Flagyl) to cover anaerobes. To cover gram negative aerobic rods (such as E. coli, or Klebsiella), the choices include an aminoglycoside, aztreomam, cefepime, or levofloxacin. You choose IV gentamicin since renal function is normal. Aminoglycosides- block protein synthesis and inhibits 30S ribosome. Bacteriocidal. IV Gentamicin/ Tobramycin - 6 mg/kg daily dosing. Pharmacy to help in dosing. Tobra >Gent for pseudomonas. Inhalation route also for bronchiectasis and pseudomonas pneumonia. Amikacin is more commonly used in children. Watch for nephrotoxicity (Gent >Tobra); especially in elderly females, and for ototoxicity. Three mechanisms of resistance: 1) reduced uptake 2) altered ribosome binding sites and 3) gene induced enzyme modifiers. Topical use also. Clinical use- oral neomycin for bowel surgery. Often used in combination with cell-wall synthesis inhibitor. Good for GU/GI infections and best against gram negative aerobes. Best Agents for Gram Negative Aerobic Rod Infections aminoglycosides, or -Aztreonam -3rd/4th generation cephalosporins (ceftazidime, ceftaz/avibactam, ceftriaxone, cefepime, ceftolozane/tazo) -Penams (imi,dori,erta,mera) -Extended-Spectrum Beta-Lactams (piperacillin-tazo and ticarcillin-clav, ampicillin-sul) -Quinolones Bacteriostatic vs. Bacteriocidal- Static antibiotics include: Chloramphenicol, Macrolides, Clindamycin, Sulfa, Trimethoprim, Tetracyclines Cidal antibiotics include: Aminoglycosides, Beta-lactams, Vancomycin, Quinolones, Rifampin, and Metronidazole. Case 2 A 32 year old female presents with vulvovaginal candidiasis. She has a “cottage cheese”, itchy, discharge. Her risks include DM and recent antibiotic use for acne. You recommend a course of oral fluconazole. Antifungals- Azoles- ketoconazole- 1st generation; mostly historical. Fluconazole (Diflucan)- 2nd generation; 150-400 mg po/IV daily. ltraconazole(Sporanox)- 3rd generation,100-200 mg bid po. Voriconazole (Vfend)-4th generation-200-300 mg po bid. 4 mg/kg IV q 12 hrs. Posaconazole- 100 mg/day po. Watch for liver toxicity, fluid retention with itraconazole, and drug-to-drug interactions. Multiple imidazole creams for dermatophytoses; clotrimazole is popular. Echinocandins- Caspofungin 50 mg/day IV. Micafungin 100 mg/day IV. Poor urine concentration. Polyenes- Amphotericin B-1-1.5 mg/kg IV daily. Watch for bone marrow toxicity, high LFTs, nephrotoxicity, phlebitis. Lipophilic Ampho. B - 5 mg/kg IV daily- less toxicity than non-lipid formulation. Terbinafine (Lamisil)- 250 mg/day po daily for onychomycosis. How anti-fungal agents work Cytoplasmic membrane- polyenes-bind ergosterol. Inhibit ergosterol synthesis- allylammines like terbinafine and azoles like ketoconazole (1st generation), fluconazole(2nd genreation), itraconazole(3rd generation), voriconazole, and posaconazole (4th generation). Watch for drug-drug interaction with the azoles. Cell wall inhibitors- echinocandins- inhibit glucan synthesis. Caspofungin, micafungin, and anidulafungin. All are IV only. Protein synthesis- flucytosine. Use for synergy, and resistant UTIs. Case 3 A 72 year old female presents to the ER with a complicated UTI with emphysematous right pyelonephritis and you are concerned about bacteremia. Urine sediment shows gram negative rods. You want to stay away from aminoglycosides since her creatinine is 1.9. Other choices include IV cefepime, levofloxacin, or aztreonam. You choose aztreonam. The following CT of the abdomen shows: Emphysematous pyelonephritis with “air” left kidney Aztreonam- a monobactam beta-lactam. Well tolerated. Narrow spectrum- gram negative aerobic rods Tribe 1 (E.coli, Proteus, Klebsiell) and Tribe 2 (Pseudomonas, Serratia, Enterobacter, Citrobacter). IV use only. Poorly absorbed and cannot be used orally. Generally not nephrotoxic. Case 4 A 40 year old obese patient with venous stasis is admitted to the hospital with fevers to 102 and a hot cellulitis of the leg. You place the patient on IV cefazolin to cover MSSA and beta-strep. Blood cultures grow Group G Streptococcus. Cephalosporins- minimal cross-over reaction with penicillins unless anaphylactic to penicillins. 1st generation- Oral- cefadroxil 500 -1000 mg daily, cephalexin 250-500 mg QlD. IV- cefazolin 1-2 gms q 8 hrs. Covers strep (except enterococcus), MSSA and Tribe 1 gram neg rods. 2nd generation- Oral- cefuroxime 750 mg BID, IV- 750 mg IV q 8 hrs.- covers bugs sensitive to 1st generation cephalosporins plus Haemophilus influenza, Pasteurella multocida. Cefoxitin 1 gm q 6 hrs. Cefotetan (watch for bleeding because of one of its side chains) 1 grm q 12 hrs- both cover anaerobes below diaphragm plus Tribe 1 gram neg rods. 3rd generation- ceftriaxone 1-2 gms q12- 24 hrs- long half life. Use in orthopedic infections-septic joints, osteomyelitis, and bacterial meningitis. Cefotaxime- used in peds. Ceftazidime for meningitis. 4th generation- IV cefepime 1-2 gms q 8-12 hrs. Covers MSSA, strep, Tribe1/Tribe 2 gram negative rods. 5th generation- ceftaroline-covers MRSA, MSSA, strep and CAP organisms. Side effects- similar to PCNs. Cefotetan- bleeding, ceftriaxone- LFTs up, and diarrhea. Later cephalosporins- ceftazidime/Avibactam- good for klebsiella pneumonia carbapenamase strains, and ceftolozane/tazobactam. Case 5 A 40 year old known alcoholic comes to the ER after his wife witnessed him having a seizure. He is SOB and chest x-ray reveals a RLL pneumonia, likely “aspiration type.” You recommend IV clindamycin for treatment. The following chest xray shows: Right lower lobe pneumonia common in Aspiration. Clindamycin- inhibits 50S ribosome. 150-300 mg po TID-QID in adults. (600 mg IV q8) Covers anaerobes above diaphragm and is a “back up” pneumococcal drug. Side effects- C. difficile diarrhea, neutropenia, increased LFTs. Steroids helpful if gastric contents are aspirated. Case 6 A 60 year old female is on chronic Coumadin(warfarin) therapy because of atrial fibrillation. She develops walking pneumonia. What antibiotics are safe for her to use without interrupting Coumadin therapy? High INRs can cause epistaxis, bleeding gums, purpura, gross hematuria, hemarthroses, adrenal hemorrhage, hemoptysis, and CNS bleeds. Coumadin Interaction- Major- sulfa, tetracycline, macrolides, quinolones, metronidazole. Minor-penicillins, cephalosporins, penams, clindamycin, aminoglycosides. Case 7 A 33 year old male heroin user who shares needles comes into the ER with MRSA bacteremia and a new heart murmur. You diagnose MRSA endocarditis and start him on Daptomycin IV for a minimum of 4 weeks. ECHO and blood work is monitored. Daptomycin-good Staph aureus drug, also enterococci and strep. Causes cell death by depolarizing the cell membrane. Used from MRSA and MSSA, especially bacteremia and right sided endocarditis, osteomylitis, soft tissue infections. Surfactant breaks medication down in lung (don’t use here). Monitor CPK. If 5-10 X CPK, consider discontinuing. Use 6-10 mg/kg/day. Only IV, and very expensive. Antibiotics Inherently with NO MRSA Acitivity -Penicillins (such as Ampicillin) -Semi-synthetic penicillins (Nafcillin) Extended Beta-lactam Agents (such as Piperacillin-tazobactam) -1st-4th generation cephalosporins (like cefazolin) -Penams (such as meropenam) Case 8 A 57 year old diabetic has PVD and a malodorous ulcer on the foot. There are signs of acute cellulitis. You are concerned about the “kitchen sink” (polymicrobial) of organisms that could be causing disease. You place the patient on Zosyn (Piperacillin-tazobactam) on admission. The following picture shows: Typical infected diabetic foot ulcer Extended beta-Lactamase Penicillins- Oral- amoxicillin-clavulanate (Augmentin) 500-875 mg bid. IV- piperacillin-tazobactam (Zosyn) 3.375 gms q6 hrs, or ticarcillin-clavulanate (Timentin), ampicillin-sulbactam (Unasyn). Continuous infusions of Zosyn have been used lately and have helped in reducing costs but still giving efficacy. Broad spectrum agents- cover anaerobes, aerobic gram – rods, enterococcus, strep and MSSA. Amox-clav.- watch for diarrhea. Piperacillin tazobactam/Ticarcillin clavulanate- “suicide” inhibitors. Watch for thrombocytopenia. No MRSA activity. Case 9 A 40 year old firefighter with a history of recurrent MRSA infections of the buttock presents with a severe cellulitis and abscess. He has a high fever, a lot of pain, and is vomiting. You admit the patient to the hospital and place him on IV Linezolid (Zyvox). Linezolid- an oxazolidinone, it blocks initial protein synthesis at the ribosomal level. Bacteriostatic rather than cidal. Very expensive, about $100.00/pill. 100% bioavailable. Watch for bone marrow toxicity (especially low platelets), serotonin syndrome (it is an MAO inhibitor) if given with SSRIs; neuropathy, GI side effects. Very good for VRE, MRSA. New oxazolidonone out in 2014 is Tedizolid. Sivextro (Tedizolid)- use 200 mg daily rather than BID and less BM dysfunction. Antibiotics That Can Be Used For MRSA (must check sensitivities) -Trimethoprim-sulfa (po or iv) -Doxycycline or Minocycline (po or iv) -Clindamycin (po or iv) -Rifampin (po or iv) -Quinolones (po or iv) -Linezolid (po or iv) -Daptomycin (po or iv) -Vancomycin (iv) -Ceftaroline (iv) -Tigecycline (iv) -Dalbavancin/Telavancin (iv) Case 10 A 40 year old female smoker presents with a one week history of an exacerbation of COPD with an increase in purulent sputum, SOB, and wheezing, with fevers. You prescribe the macrolide azithromycin with prednisone. Macrolides- block 50-S ribosome. Erythromycin (one of the originals)- 333 mg tid for adults but GI side effects. Extended macrolides- Clarithromycin (metallic taste) po- 250- 500 mg bid or Azithromycin- 500 mg bid x day 1, then daily for 4 days. 63 hour half-life. Watch for drug-drug interactions; liver metabolism. Good for respiratory tract pathogens (S pneumo sensitivities are slowly worsening, H.flu, Moraxella catarrhalis, Mycoplasma, Chlamydiophila, Legionella) and MAI (atypical TB). Azithromycin IV is now used by general surgeons in patients who need bowel motility. Case 11 A 21 year old sexually active female presents with a smelly (like dead fish), vaginal discharge. She has a positive “whiff” test and vaginal stains show clue cells. You diagnose BV (Bacterial Vaginosis) and place her on metronidazole. The next day, you are working in the health department and diagnosis a Trichomonas vaginal infection and treat the patient with metronidazole also. Metronidazole- nitroimidazole class. Acts by forming thio-ether bonds with cysteine-containing enzymes by being reduced to nitroso intermediates. Best anti-anaerobic antibiotic below diaphragm. Poor lung penetration. Good for certain protozoa- E. histolytica, trichomonas, giardia. Good for C. difficile diarrhea and rosacea, bacterial vaginosis (BV). Adverse effects- bad taste, disulfiram reaction with ETOH, CNS changes or neuropathy, GI side effects. Dosing- 500 mg tid po/iv. Case 12 A 32 year old female comes in with recurrent HSV progenitalis. She gets recurrences every 2-3 months on the vulva. You recommend a daily prophyllaxis with Acyclovir 400 mg po. Nucleoside inhibitors- for herpes simplex virus HSV 1 or HSV 2 and HZV. Acyclovir- (prodrug famciclovir); pencyclovir (prodrug valacyclovir). Case 13 A 65 year old patient in the hospital has just had CABG-4 surgery 3 days ago. You are called to see him for a new pulmonary infiltrates bilaterally, SOB, fevers to 102.5, WBC of 23,000, left shift. Yellow sputum production is growing Serratia marcesans on culture. You order Merapenam IV and respiratory treatments. The following chest xray shows: HCAP- bilateral lower lobes from Serratia Penams- Imipenam 500 mg q 6 hrs, Merapenam-1 gm q 8 hrs, Doripenam. Ertapenam- 1 gm q 24 hrs. Broad spectrum; especially resistant gram negative aerobes/anaerobes, MSSA and strep. No MRSA or enterococcal coverage. Newer agent- Doripenam- more pseudomonas coverage. Imipenam can cause seizures. Penams are good for ESBL (extended spectrum beta-lactamase producing gram neg rods) Case 14 A 12 year old child comes to see you with a severe sore throat and tonsillitis, with malaise and fevers. On physical exam, she has an acute tonsillitis. Strep screen is positive. You order Amoxicillin for Rx. The following picture shows classic: Purulent tonsillitis from group A Beta-streptococcus Penicillins- cell wall inhibitor. Oral-amoxicillin 500-875 mg BID. IV-ampicillin 1-2 gms q 6 hrs. Good for beta-Strep. Benzathine Pen G still used for syphilis. Side effects- all penicillin derivatives- skin rash, rare anaphylaxis. Case 15 A 24 year old pregnant female gets very sick with fevers, chills, and a UTI. You recommend nitrofurantoin for the E. coli on culture. Antibiotics Generally Safe in Pregnancy: -Penicillins -Cephalosporins -Macrolides (except Clarithromycin) -Nitrofurantoin (avoid during 3rd trimester) -Tri-sulfa (OK during 2nd trimester) Pregnancy- Contraindicated- tetracyclines, quinolones. (also in pediatrics), Flagyl. Safe- beta lactam agents, nitrofurantoin, and macrolides (except clarithromycin). Case 16 A 45 year old previously healthy male presents to the hospital with a serious lobar pneumonia and fevers to 102. He is breathing 35 times/min and his BP is 100 systolic. You admit him to the medical floor and place him in the CAP protocol, including Levaquin (a third generation quinolone) 750 mg IV daily. Quinolones- act by blocking DNA gyrase and topoisomerase enzymes. Broad spectrum but poor anaerobic coverage except moxifloxacin. 1st generation- naladixic acid- historic only. 2nd generation- ciprofloxacin 250-750 mg po bid, or 400 mg iv bid. Ofloxacin- 400 mg bid po. Good for Tribe 1 gram neg rods and some Tribe 2 organisms like Pseudomonas. Used for traveler’s diarrhea. Fair against respiratory pathogens. 3rd generation- levofloxacin- the L isomer of ofloxacin. Respiratory floroquinolone. Excellent for pneumococcus and atypical pathogens. Fair for UTIs. Good gram neg rod coverage. 4th generation- moxifloxacin- coverage like that of levofloxacin plus anaerobes above/below diaphragm. Adverse effects- CNS changes in the elderly, photosensitivity, prolongation of the QT interval. Contraindicated in pregnancy and pediatrics because of tendonopathy. Case 17 A 76 year old patient has a prosthetic knee infection secondary to Staph epidermidis sensitive to cephalosporins. The prosthesis is retained after surgery. You treat her with 6 weeks of IV Ceftriaxone and Rifampin 300 mg/day (then cefadroxil and Rifampin po indefinitely). Rifampin (rifampicin)- has excellent intracellular killing. Good for synergy against staph (MSSA and MRSA), pseudomonas. Excellent when a prosthesis is present. Penetrates biofilms well. Don’t use as mono-therapy. Anti-tuberculosis drug for decades. Acts by inhibiting DNA dependent RNA synthesis by blocking RNA polymerase. Turns the urine red-orange! Monitor LFTs. Semi-synthetic rifampicins include rifabutin (Mycobutin) which is used in resistant Mycobacterial disease, has less drug interactions, rifapentine, and rifaximin (Xifaxan). Also in the Rifampin Class of Medications Rifabutin (Mycobutin)- dosing is 150 mg po bid or 300 mg daily Rifapentine is used in latent TB on a weekly dosing schedule Rifaximin (Xifaxan) is poorly absorbed and big $. Used in IBS, bacterial overgrowth, traveler’s diarrhea Rx. Dose- 200 mg tid to 550 mg bid. Case 18 A 33 year old male with Type 2 DM presents with acute MSSA cellulitis of the leg with positive blood cultures. You start him on Nafcillin IV in the hospital. Semi-Synthetic Penicillins- Oral- dicloxacillin 250-500 mg QID. IV- nafcillin 1-2 gms q 4 hrs, or oxacillin IV, good for Strep (except enterococcus) and MSSA. Side effects- interstitial nephritis, phlebitis, increased LFTs with oxacillin. Case 19 A 28 year old high risk male presents with acute interstitial pneumonia secondary to Pneumocystis jeroveci. HIV comes back positive on Western Blot. You start him on IV Trimethoprim-Sulfamethoxasole with IV steroids and he promptly improves over 5 days. Sulfamethoxazole (Tri-sulfa)- bacteriostatic. Blocks synthesis of bacterial tetrahydrofolic acid. Sulfa is a structural analog of PABA (para-aminobenzoic acid), an intermediate in the bacterial production of folate. Trimethoprim binds to dihydrofolate reductase preventing production of THF. Good for most E.coli, MSSA, MRSA, Pneumocystis jeroveci. Rash in 15%; Stevens-Johnson syndrome is rare. Case 20 A 30 year old male presents with fevers to 2 weeks, muscle pains, headache and a petechial rash. During a recent hunting trip he pulled an imbedded tick off his axilla. You suspect Rocky Mountain Spotted Fever and start him on tetracycline. Tetracyclines- inhibit 30S ribosome. Bacteriostatic. QID dosing hard for compliance. Contraindicated in children and pregnancy. Doxycycline is bid; cyclines can cause esophagitis, photosensitivity, drug-induced lupus. Minocycline is one/day; watch for vertigo. Tigecycline- IV only. Cidal, broad spectrum, covers MRSA well, pneumococcus, and anaerobes. Has fallen into disfavor because of deaths attributed to it. Mnemonic for site of action of Protein synthesis antibiotics: 50S ribosome- CH-ERY-L- Choramphenical, Erythormycin (macrolides) and Lincomycin (clindamycin) 30S ribosome- AM-TET- Aminoglycosides, Tetracyclines Linezolid binds to the 23 S portion of the 50S ribosome. Case 21 A 45 year old female presents with a complicated MRSA UTI with pyelonephritis. She develops bacteremia and is placed on Vancomycin. After 5 days of treatment, she develops ataxia, a dreaded side effect of vancomycin. Watch for Vancomycin-intermediate Resistant Staph (VISA) and VRSA. VRE is already a problem. Vancomycin- 15 mg/kg/dose q 12 hours. Concentration dependent. Acts on cell wall synthesis. Pharmacy to dose. For MRSA, if MIC>2; don’t use. IV good for most gram positives, but no anaerobic or gram neg aerobe coverage. Watch for red man (neck) syndrome- histaminic reaction with rapid infusion. Also nephrotoxic and ototoxic. PO dosing not absorbed- good for C.difficile (125-500 mg). Good Rx for penicillin allergic pts. for Enterococcus faecalis, especially for bacteremia. Dalbavancin came out in 2014, and has a longer half life than Vancomycin. Can be used weekly. Case 22 A 40 year old male has a VAP from a Klebsiella pneumoniae organism that is a carbapenamase (KPC). You suggest Colistin (Polymyxin E) inhalation for treatment. How does Colistin work and what are its potential side effects? Colistin (polymyxin E) is a bactericial drug that binds to lipolysaccharides in the outer cell membrane of Gram-negative aerobic bacteria (CRE, Pseudomonas and A. baumanii) allowing disruption and leakage of cell contents, and death. It causes reversible nephrotoxicity and neurotoxicity. It can cause vertigo, weakness, and paresthesias. Inhalation dose is 50-75 mg in NS via neb 2-3x/day. Especially good in cystic fibrosis pts. It is not active against Proteus. IV dose- 1.5-5 mg/kg/day, pending on CrCl. 1. What is the only antibiotic/antibiotic class that targets Topoisomerase in bacterial cells? A.) Aminoglycosides B.) Beta lactams C.) Ethambutol D.) Quinolones E.) Trimethoprim 2. A 11 year-old boy presents to the ED with diffuse abdominal pain with rebound tenderness and a positive McBurney’s sign. Which two medications would you place this patient on to cover both anaerobes and gram negative aerobic rods? A.) Clindamycin and Ciprofloxacin B.) Clindamycin and Gentamicin C.) Metronidazole and Tobramycin D.) Metronidazole and Aztreonam E.) Metronidazole and Levofloxacin F.) B, C, D G) Metronidazole and Burnamycin 3. A 65 year-old female is being treated for a systemic fungal infection with a polyene antimycotic agent that binds ergosterol. Which of the following will reduce the adverse effects often experienced with this agent? A.) administer with clavulanic acid B.) administer with fluconazole C.) administer the lipid formulation D.) administer the protein formulation E.) administer with terbenafine F.) administer with a martini 4. An 83 year-old female presents to the ED from her extended care facility with change in mental status, dysuria, and flank pain. The patient is febrile with a temperature of 102. Past medical history is significant for neurogenic bladder and renal artery stenosis. Which antibiotic would cover systemic gram negative bacilli infections without affecting renal function substantially? A.) Aztreonam B.) Gentamycin C.) Metronidazole D.) Tobramycin E.) Terbinafine F.) Nephrocillin 5. A 24 year-old male is being treated for gonococcal urethritis. When asked about his allergies, he responds that he is allergic to penicillin. Which adverse reaction to penicillin would disallow the administration of ceftriaxone? A.) anaphylaxis B.) elevated liver function tests C.) diarrhea D.) rash E.) tendonopathy F.) Halatosis fugax 6. A 7 year-old was bitten at daycare by a 4 year-old. What is the drug of choice for treatment? A.) Ampicillin B.) Cefuroxime C.) Biteadroxil D.) Cephalexin E.) Gentamycin F.) Vancomycin 7. A 46 year-old homeless male with a history of alcoholism and IV drug abuse presents to the ED with a change in mental status, headache, nuchal rigidity, and fever/chills. He refuses an HIV test, but his CD4 count is 82. You suspect Cryptococcal meningitis. Which medication should be utilized? A.) Echinocandins B.) Fluconazole C.) Itraconazole D.) Ketoconazole E.) Cryptoconazole F.) Voriconazole 8. A 82 year-old female with a history of GERD and dysphagia is seen by her PCP with SOB and consolidated crackles in the left lower lobe. Chest X-ray reveals a LLL pneumonia. Which medications are necessary for the treatment of chemical pneumonitis? A.) Clindamycin B.) Doxycycline C.) Steroids and Clindamycin D.) Steroids and Doxycycline E.) Vancomycin 9. A 55 year-old female who recently underwent a total knee replacement (on Coumadin) develops cystitis and is placed on Bactrim. The patient returns to your office for follow-up concerned about her bleeding gums, nose bleeds, and large bruises surrounding her joints bilaterally. Which medication can you switch this patient to reduce her drug interaction? A.) Erythromycin B.) Ciprofloxacin C.) Cefadroxil D.) Bruisacillin E.) Levofloxacin F.) Metronidazole 10. A 25 year-old female allowed her partner to inject heroin into her calf muscle and has now developed cellulitis. The patient also complains of fever/chills, headache, and heart palpitations. What antibiotic will effectively treat her bacteremia and cellulitis? A.) Amoxicillin B.) Clindamycin C.) Doxycycline D.) Rifampin E.) Vancomycin 11. A 6 year-old boy and his parents present to your office with a 4-day history of oily, foul smelling diarrhea, after coming back from a camping trip. The parents and child need to be treated before they can take their son back to daycare. Which medication is most appropriate? A.) Clindamycin B.) Itraconazole C.) Ivermectin D.) Loperamide E.) Metronidazole F.) Foulsmellacin 12. What is the recommended daily prophylactic dose for HSV-2 infections in adults? A.) Acyclovir 200 mg po daily B.) Acyclovir 400 mg po BID C.) Acyclovir 600 mg po daily D.) Valacyclovir 400 mg po BID E.) Valacyclovir 600 mg po BID 13. A 35 year-old firefighter who sustained third-degree burns from an industrial fire 2 week ago has grown Pseudomonas from his bronchial washings and burn cultures. Which penam antibiotic has the best pseudomonas coverage? A.) Doripenam B.) Ertapenam C.) Imipenam D.) Merapenam E.) Obamapenam 14. A 76 year-old female who recently returned from a trip to Australia presents to your office with a large, gaping wound in her foot that she got from stepping on a piece of coral on the beach. She did not want to seek medical attention in another country and did not know how to properly clean and dress the wound. Her right great toe has a large, deep pyogenic ulceration with foul-smelling grey discharge. The patient refuses to be admitted to the hospital. What broad spectrum antibiotic can be given orally in an outpatient setting? A.) Augmentin B.) Timentin C.) Unasyn D.) Zosyn E.) Zyvox 15. A 58 year-old male patient is being treated for a severe MRSA cellulitis and associated abscess with Linezolid. What is a serious side effect associated with this medication? A.) Anaphylaxis B.) GI disturbance C.) Hepatic encephalopathy D.) Hypercoagulability E.) Thrombocytopenia F.) Turning purple into green poka-dots 16. A 28 year-old G2P1001 at 35 weeks’ gestation presents with dysuria, polyuria, fever, chills, and a temperature of 101. What antibiotic class is absolutely contraindicated during pregnancy and why? A.) Cephalosporins- CNS malformations B.) Penicillins- infantile cataracts C.) Macrolides- hydrops fetalis D.) Quinolones- tendon dysgenesis E.) Sulfonamides- bone deformities 17. A 62 year-old female presents with recurrent UTIs. The patient is allergic to penicillins with an anaphylactic reaction. What medication would be most appropriate for this patient? A.) Cefepime B.) Ciprofloxacin C.) Levofloxacin D.) Moxifloxacin E.) Rifaximin F.) Elderacillin 18. A 35 year-old professional skier developed edema and erythema surrounding his incision post-total knee replacement on post-op day 25. There is evidence the infection spread to the hardware, which is removed and cultured. What is the appropriate treatment to cover MRSA in this situation? A.) ceftriaxone and amoxicillin B.) ceftriaxone and rifampin C.) vancomycin and amoxicillin D.) vancomycin and ceftriaxone E.) vancomycin and rifampin 19. A 5 year-old boy presents to your office with a large, red lesion that continues to spread, according to the patient’s mother. The lesion is now 6 cm in diameter with central and peripheral erythema. The patient had recently gone deer hunting with his father, who denies any signs of a rash. The patient has no other symptoms. What medication would you treat him with? A.) Amoxicillin B.) Ceftriaxone C.) Doxycycline D.) Terbinafine E.) Tetracycline 20. Match the following drugs to their known side effects: 20.) Amphotericin B A.) Turning red with infusion 21.) Aminoglycosides B.) Bleeding 22.) Azoles C.) Bone marrow toxicity 23.) Cefotetan D.) C. Diff colitis 24.) Clindamycin E.) Disulfiram-like reaction 25.) Metronidazole F.) Hepatic toxicity 26.) Vancomycin G.) Ototoxicity Answers: 1. D 2. F 3. C 4. A 5. A 6. B 7. B 8. C 9. C 10. E 11. E 12. B 13. A 14. A 15. E 16. D 17. B 18. E 19. A 20. C 21. G 22. F 23. B 24. D 25. E 26. A Basic Microbiology Bacteria- bacteria are prokaryotes with free circular DNA, ribosomes, no mitochondria or nucleus, and a peptidoglycan cell wall. Gram negative bacteria have a periplasmic space and outer membrane. The doubling time for most bacteria is 20 minutes, but 24 hours for M. tuberculosis. MICs (Minimal Inhibitory Concentrations)-this is the main way we clinically determine antibiotic sensitivities. A MIC panel is generated for potentially pathogenic isolates. We like to pick “S” (Sensitive) antibiotics rather than “R” (Resistant) antibiotics. You can’t compare the MICs of different antibiotic classes; only the same class. In Vitro Susceptibility Testing “S” for Sensitive- favorable “I” for Intermediate- who knows “R” for Resistant- unfavorable Minimum Inhibitory Concentrations (MIC)- The following schematic shows: Macrobroth Dilution; Lowest concentration of an antibiotic that prevents visible evidence of growth after 20-24 h exposure = MIC Gram Stain- invented by H. Christian Gram in the late 1800’s to help identify bacteria. Fungi-they are eukaryotic and have a nucleus with a nuclear membrane and the cytoplasm contains mitochondria, Golgi apparatus, lysosomes and an endoplasmic reticulum. Morphology is either small round yeasts, or filamentous molds with a mycelium of hyphae. Dimorphic fungi have a yeast form in tissues and an environmental mycelial form. Fungi cause disease by mycotoxins, hypersensitivity or invasive infection with tissue damage. Cell mediated immunity is the most important defense. Viruses-“poisonous fluid” (Latin)- viruses can replicate only in a host cell and cannot survive long outside a host cell. They consist of a central genome of either RNA or DNA, and a protein capsid shell or outer envelope. The genome is either double stranded DNA or single stranded RNA, linear or circular, one piece or segmented. Viral envelopes are lipoproteins, often with glycoprotein spikes. The Herpes virus group is the most common group of viruses (nine total now) that are seen clinically: Divided into 3 groups: the alpha, the beta, and the gamma. Alpha herpesviruses include herpes simplex 1 and 2, and viricell-zoster virus (VZV; HHV-3). Beta herpesviruses include cytomegalovirus (CMV; HHV- 5), HHV-6A and HHV-6B and HHV-7. The gamma herspviruses include Epstein-Barr virus (EBV; HHV-4) and Kaposi’s sarcoma-associated herpesvirus (HHV-8). Protozoa- all are unicellular with eukaryote cellular structures. They have a fragile trophozoite stage and most have a resistant cyst form. All have life cycles outside the human host, and most can multiply in humans. Infection is by ingestion, by inhalation, by insect bite or by intercourse. Eosinophilia is not found in protozoal infections, but it is in metazoal (worms- nematodes, trematodes, and cestodes) infections. Protective immunity is poorly developed in most protozoal infections. Case 23 A 40 year old male presents with septic shock. He is recently post op cholecystectomy and has a skin-wound infection. Blood cultures grow Staph aureus, a gram positive coccus, and you suspect Toxic Shock Syndrome secondary to TSST (toxic shock syndrome toxin). Gram Positive Cocci-Clusters- CLUSTERS on gram stain- Staphylococcus aureus (MSSA or MRSA) cause skin infections/abscesses, bacteremia/shock. Contain protein A and teichoic acid in cell wall. Coagulase positive. Encapsulated, slime production. Toxins include cytotoxins(5)- alpha through episolon. Also exfoliative toxin, toxic shock syndrome toxin (TSST-1= enterotoxin F, exotoxin C), enterotoxins 1-f. MRSA-can produce PVL(Panton- Valentine-Leucocidin) toxin- causes the organism to “dig deep” into tissue. Staphylococcus epidermidis- > 200 strains- associated with prosthetic device infections by adhesion. Low virulence. Micrococcus – rare, but seen in lung infections, deep tissue infections occasionally. Staphylococcal Infections- Staph aureus are coagulase +. Staphylococci are found in bunches on gram stain and are gram + cocci (Staph means “bunches of grapes” in Greek). 65% are MSSA sensitive to cefazolin or Nafcillin or oxacillin. 35% are MRSA. This is variable geographically. Staph epi contain over 100 different strains. They are coagulase --, and 50% are resistant to cefazolin or Nafcillin, and look like MRSA on sensitivities. They cause the majority of prosthetic device infections. Staphyloccocus Coagulase Negative Prosthetic Devices Associated (subtypes) with Staph Coag Negative Staph epidermidis Staph hominis CNS shunts Staph capitis Prosthetic valves Staph saprophyticus Pacemakers Staph lugdunensis Breast implants Staph warneri Gortex Vasc. Grafts Staph haemolyticus Artificial Joints Non biological mesh Biological meshes- Surgisis/Permacol/Xenmatrix/Strattice- porcine dermis. These do not become infected easily. Parietex (polyester synthetic) has more trouble. Case 24 A 82 year old male comes into the ER with fevers and chills for 7 days. He has gross hematuria and dysuria. On physical exam, his prostate is tender and urinalysis shows 50 WBC/HPF and 3+ bacteruria. Spun down gram stain of the urine shows gram positive cocci in chains. Blood cultures subsequently grew Enterococcus faecalis, a gamma streptococci. Gram Positive CHAINS on Gram stain-Alpha-Streptococci-Strep viridans group- endocarditis and pneumonia, Strep. pneumoniae- seen as diplococci; virulence by being encapsulated. Produces pneumolysin, neuraminidase, and purpura-producing principle. Causes #1 pneumonia in USA, also meningitis, DIC, and endocarditis. They partially hemolyze blood agar. Beta Streptococci- Groups A (Strep. Pyogenes, M protein is anti-phagacytic. Produces streptolysin O, streptolysin S, DNAses, streptokinases, hyluronidsases, and erythrogenic toxins), B (Strep. agalactiae),C, and G-skin/soft tissue infections. Extremely virulent. They fully hemolyze blood agar. Gamma Streptococci- Enterococcus species (faecalis, faecium, VRE) - UTls, abdominal abscesses, endocarditis. Often not a pathogen in polymicrobial environment. Usually sens. to Ampicillin, Vanco, Dapto. They do not hemolyze blood agar. Pneumococci-(Strep pneumoniae)- 3 main complications of bacteremia are DIC, meningitis, and endocarditis. 3 main complications of Pneumococcal pneumonia are pericarditis, empyema, and lung abscess. If bacteremic, be sure to add a macrolide (dual therapy) which helps to inhibit pneumolysin production. Pneumococci Virulence Factors- polysaccharide capsule resists phagocytosis. Lack of activation of alternative complement pathway. Surface protein A- inhibits complement activation. Pneumolysin, cytotoxin, activates complement system. Enzymes- autolysin, neuraminidase, hyaluronidase enhance adhesion and release of pneumolysin. Spread after colonization- upper and lower respiratory tracts by direct invasion (non-invasive)- sinuses, bronchi, eustachian tubes. Reach normally sterile areas by hematogenous spread (invasive). Blood, peritoneum, CSF, joint fluid. Summary of Gram Positive Cocci- MSSA, MRSA, Staph epidermidis, Alpha- strep (Strep viridans group, Strep pneumo), Beta-strep (Groups A,B,C,F,G), Gamma-strep- Enterococcus faecalis/faecium, VRE. Case 25 A 40 year old male with history of alcoholism presents to the ER with fevers, delerium, and stiff neck. Lumbar puncture shows a cell count of 2000 with a left shift, a glucose of 10, and a high protein. Gram stain shows gram positive rods, and cultures grow Listeria monocytogenes. Rx of choice is Ampillin. Aerobic Gram Positive rods- Listeria monocytogenes - causes bacteremia and meningitis. Intracellular pathogen. Invades pregnant women, newborns, and alcoholics who have chronic liver disease. Corynebacteria- diphtheria. Potent exotoxin. Other corynebacterial infections in device-related nosocomial infections. JK strain seen in febrile neutropenics. Bacillus species (anthracis- Anthrax has an antiphagocytic capsule and 3 toxins- protective factor, edema factor and lethal factor) Spore formers and soil and animals are the reservoirs. Bacillus cereus an occasional pathogen. Erysipelothrix rhusiopathiae- found in animals and on fish and can cause erysipeloid. Case 26 A 65 year old male with COPD from smoking presents to the ER with SOB, fevers, cough and a CAP. Gram stain shows gram negative diplococci and cultures grow Moraxella catarrhalis. Aerobic Gram Negative diplococci- Neiserria gonorrhea – causes urethritis/cervicitis. Often intracellular. Neiserria meningitidis- not inhibited by serum- causes acute meningitis and sepsis. Moraxella catarrhalis- URIs, CAP. Kingella- associated with endocarditis, septic joints in pediatric patients. Acinetobacter- nosocomial pathogen. Case 27 A 55 year old banker presents to the ER with difficulty speaking and swallowing, and severe pain and fever. Lateral neck x-ray shows the “thumb” sign. Direct laryngoscopy by ENT reveals epiglottitis, and you suspect Haemophilus influenza, a gram negative coccobacillus. Aerobic Gram negative coccobacilli- Haemophilus influenza- epiglottis, pneumonia, cellulitis in peds. Has an anti-phagocytic capsule and endotoxin. Rx- 2nd and 3rd generation cephalosporins. (also H. parainfluenza) Also Bordetella (pertussis)- produces 4 exotoxins, and an endotoxin, and Legionella pneumophila (causes mild Pontiac fever or the lethal Legionnaire’s disease)- is an intracellular pathogen. Case 28 A 53 year old internist presented to the ER with RUQ abdominal pain and acute gallstone pancreatitis (amylase was over 400). Blood cultures grew Escherichia coli (E.coli) sensitive to cefazolin. He was promptly taken to surgery for a laparoscopic cholecystectomy. E.coli is considered a Tribe #1 aerobic gram negative rod. Aerobic Gram Negative rods- many contain endotoxin, capsular K, flagellar H and somatic O antigens which provide virulence. Tribe #1- E.coli, Proteus mirabalis, Klebsiella pneumoniae or K. oxytoca. Common cause of UTls, abdominal infections. Generally sensitive to cefazolin. Tribe #2- Pseudomonas (“grape odor”, exotoxin A, exoenzyme S, produces elastase, leucocidin, phospholipase C), Citrobacter, Enterobacter, Serratia, Alcaligenes (Achromobacter), Kluyvera- all more resistant. Cause nosocomial infections, especially lung and urine. Treat with Cefepime or Zosyn. Oxidase + gram – rods- Vibrio (cholera), Campylobacter, Helicobacter (associated with PUD, gastric cancer), Aeromonas. Other- Eikenella corrodens- seen in dental and human bite infections. It is resistant to clindamycin and metronidazole, but sensitive to penicillins. E. coli Clinical Syndromes (4 main types)- Enteric Infections-Traveler’s Diarrhea. Childhood diarrhea-Hemorrhagic colitis/HUS. Shigella-like dysentery. Cholecystitis and cholangitis-obstruction --> stagnation --> bacterial overgrowth. Intra-Abdominal abscess- due to perforated viscous, abscess, cholecystitis, or ascending cholangitis. Bacteremia also. Proteus: A.K.A. “the Swarmer”- this organism is part of the TRIBE I group, usually P. mirabilis.. It swarms on culture medium. It smells like musty, dirty socks. It takes part in UTIs, intra-abdominal infections, pneumonia, and wound infections. Some of the species (i.e. P.vulgaris) are resistant to cefazolin. Case 29 A 26 year old female with poor dentition presents to the ER with severe anterior neck pain and swelling. Clinically, you suspect a submandibular abscess and Lemiere’s Syndrome (septic jugular phlebitis) from Fusobacterium necrophorum and other mouth anaerobes. You are concerned about the development of mediastinitis because of bacteria traversing distally in the pre- vertebral space. You suggest surgery for I&D and IV Clindamycin. Anaerobes above the diaphragm- Gram pos cocci- Peptococcus/ Peptostreptococcus (also found in vagina, skin) - “bad breath” organisms; live on gums. Gemella morbillorum. Gram neg diplococci- Veillonella. Gram neg rods- Prevotella species (such as P. oralis, bivia, melanogenica), Fusobacterium (necrophorum), other Bacteroides. Most anaerobes above diaphragm are sensitive to penicillin or clindamycin. Gram pos rods- Lactobacillus, Propioni bacterium acnes (associated with acne), and Eubacterium species. Case 30 A 70 year old woman presents to the ER with severe abdominal pain from a perforated colon secondary to acute diverticulitis and pericolonic abscess. Blood cultures grow Bacteroides fragilis, gram negative anaerobic bacillus. She is brought to emergency surgery for partial colon resection. Anaerobes below the diaphragm- anaerobe/aerobe ratio is 1000:1 in stool. Gram neg rods - Bacteroides fragilis- most common pathogen in the gut. Causes abscesses. Gram pos rods- Clostridia species. C. septicum- associated with GI malignancies. C. perfringens- gas gangrene, C. botulinum- botulism, C. tetani- tetanus, C. difficile- associated with pseudo membranous colitis. Spread by spores. Most anaerobes below diaphragm sensitive to metronidazole, or Zosyn/Timentin, or Meropenam/Ertapenam or cefoxitin, more than clindamycin. Case 31 A 40 year old Marine veteran presents with a draining sinus on his left jaw associated with jaw swelling and pain. You suspect the pathogen is Actinomyces, a gram positive anaerobic rod. Actinomyces- gram postive anaerobic rod - (A. israelii), causes “lumpy” jaw (osteomyelitis), abdominal, mycetoma, and thoracic infections, sometimes CNS infections. Look for sulphur granules. Also causes PID from IUD use. Rx- penicillin. Tropheryma whippelii- an actinomycete causing Whipple’s disease. Case 32 A 52 year old construction worker who frequently kneels while working presents with a large draining mass of infected tissue from his left lower leg, associated with pain and low grade fevers. I&D reveals a mycetoma and cultures grow Nocardia asteroides, a gram positive, filamentous rod, weakly acid fast. Nocardia asteroides- gram positive filamentous rod, weakly acid-fast aerobic soil bacteria. Causes pulmonary pseudo- tuberculosis, brain abscesses, and mycetomas in soft tissue after soil exposure. Often suppuration and scarring. Rx with sulfa. Case 32 A 40 year old outdoorsman presents with a FUO. He has muscle pains, arthralgias, headaches, diarrhea, and cough, and slight confusion. His wife pulled a tick off of his groin 2 weeks ago after a camping trip. You suspect Ehrlichiosis, one of the Rickettsiaceae organisms. Rickettsiaceae– small gram neg bacilli, includes Rickettsia, Orientia, Coxiella, Anaplasma and Ehrlichia. They have a cell wall, prokaryotic ribosomes, RNA, DNA, and have peptidoglycan in the cell wall. Unlike bacteria, they lack enzymes for energy metabolism, hence they are obligate intracellular parasites, and can’t replicate extracellularly. Virulence factors- contain lipopolysaccharide, mild toxins, phospholipase A, and intracellular replication causing host cell death. R. rickettsii- Rocky Mountain Spotted Fever. Ehrlichia- tick borne Ehrlichiosis. Anaplasmosis- tick borne or iatrogenic spread through surgery, or tattoos. Case 33 This microorganism is spread by body lice and caused more than 1 million infections in infantry men during World War I; called Trench Fever. Symptoms were fevers, malaise, rash, diarrhea, total body ache, and thrombocytopenia lasting for up to 4 weeks. Bartonella quintana was the bacteria. The following picture shows a body louse. Bartonellae- similar to Rickettsiaceae. They will grow in cell-free cultures. B bacilliformis- Oroya fever- spread by sand flies. B. henselae- cat scratch disease, bacillary angiomatosis in HIV. B. quintana- Trench fever, famous in World War 1-spread by body lice (Pediculus humanus). Case 34 A 43 year old hunter from central Wisconsin presents to you with Bell’s Palsy. You order ELISA testing and Western Blot and they are positive for Lyme’s Disease. Borrelia burgdorferi is the spirochete and the deer tick is the vector. You recommend treatment with 30 days of Doxycycline. Spirochetes – corkscrew appearance. Treponema pallidum; causes syphilis. Borrelia burgdorferi- causes Lyme disease, found in northern hemisphere in many locations, B. recurrentis- causes Relapsing Fever, Leptospira-associated with infected animals (rodents) or their urine. Case 37 You are working as a “prompt care” doctor in Little Rock, Arkansas. Ticks and deer flies have been heavy in the area. A 40 year old hunter who has been recently “skinning” rabbits presents with high fevers, lethargy, anorexia, and with a bite region on the arm with associated painful lymphadenopathy. Some of his lymph nodes have suppurated (like plague). His face is edematous and his conjunctiva are erythematous. You suspect Tularemia. To culture F. tularensis -use buffered charcoal and yeast extract Humans contract tularemia by handling diseased carcasses, eating undercooked meat of diseased animals, or being bitten by certain deer fly or tick vectors. There is a pneumonic form. Zoonotic bacteria – bacteria that cause human diseases but have an animal or bird reservoir. Pasteurella multocida- gram neg rod ; infects humans via dog/cat bite. Brucella- gram neg coccobacillus- humans infected by unpasteurised milk/cheese. Yersinia- gram neg rod; Y. pestis causes plague. Carried by fleas. Francisella- gram neg coccobacilli; F. tularensis causes tularemia. Spread by rabbits, rodents, or ticks/deer flies. Epicenter in the US is Missouri, Arkansas, and Oklahoma. Has been used as a biowarfare agent. Chlamydophila psittaci (Parrot fever or ornithosis) is spread by sick birds (parrots, macaws, etc); and causes atypical pneumonia. Case 36 A 30 year old HIV patient with a history of non-compliance and a CD4 count of 180 presents with difficulty swallowing. EGD shows the “cottage cheese” plaques and dimorphic fungus Candida is suspected; and esophagitis is diagnosed. You treat with Fluconazole. Fungi- most common pathogens are dimorphic (yeasts/molds) Candida species (>150 types). C. albicans by far most common > C. tropicalis, C. parapsilosis, C. lusitaniae. Torulopsis (Candida) glabrata and C. krusei are most resistant to imidazoles. Mucormycosis- causes invasive sinus disease in diabetics. Other dimorphic organisms- Aspergillus, Histoplasma capsulatum, Cryptococcus neoformans, Blastomyces hominis, Coccidiomyces imitis, and Sporothrix schenkii. Can use serologies and urine antigen screens for some to help in diagnosis, but biopsy usually best. Case 37 An 18 year old Indian male has had Leprosy (Mycobacterium leprae) for over 10 years. He presents with an infected right foot and “auto-amputation” of the part of the foot and hands from peripheral neuropathy. Mycobacteria- non motile, non-spore forming, strictly aerobic rods. Intracellular bacteria. Cell wall has waxy lipid layer. Acid fast stain (Kinyoun) or auramine-rhodamine fluorescent stain for diagnosis. Intracellular, slow growing, causing granuloma with caseation(cheese like). M. tuberculosis and M. leprae (Leprosy) are most common. Fast growers are atypical TB- MAI, M. abscessus, M. marinum (sensitive to sulfa), M. gordonae, M. chelonae, M. fortuitum. M. chelonae and M. fortuitum-associated with sternal wound infections. The following picture shows M. marinum carbuncular lesions sustained from a fishhook injury. Case 38 A 10 year old female has had a “bug” going around in her large family over the last week. Her brothers have been sick with fevers and cough, as well as her older sister. She presents to you with a painful ear, and fullness with decreased hearing. You suspect Mycoplasma pneumoniae, as bullous changes are present. Mycoplasma/Ureaplasma- smallest free living organisms; about 0.2- 0.7 microns. No cell wall, so doesn’t show ongram stain. Slow growing. Ureaplasma- causes NGU (non-gonococcal urethritis). M. pneumonia cause URIs (including bullous myringitis), transverse myelitis, erythema multiforme, hemolytic anemia. M. hominis- causes UTIs, and PID. Associated with infertility. Case 39 A 25 her old sexually active white female with multiple partners presents to the health department for treatment of pelvic pain and vaginal discharge. PE shows acute cervicitis, and PCR reveals Chlamydia trachomatis. She is treated with doxycycline. One month later, she presents to her internist with severe low back pain, conjunctivitis, and a rash on her feet. You suspect Reiter’s Syndrome (an autoimmune reactive arthritis) as a reaction to her previous Chlamydia cervicitis. Keratoderma blenorhagicum can be part of this syndrome. Chlamydia- small, obligate intracellular bacteria. Have a cell wall, RNA and DNA. Unlike bacteria, they have no peptidoglycan in their cell walls, can’t synthesize ATP, and have a dimorphic life cyle. The first form is the elementary body and the second is the reticulate body. Causes non-gonococcal urethritis (NGU), trachoma (most common cause of blindness in the non-western world), LGV (lymphogranuloma venereum), psittacosis (Parrot fever), and C. pneumonia-now Chlamydophila (atypical pneumonia, especially in sickle cell patients; called Acute Chest Syndrome). Case 40 A 50 year old male with profound mental retardation and a brain injury at birth lives in a long term care head injury center. He has a PEG tube and chronic suprapubic catheter. He battles recurrent serious UTIs and pyelonephritis. A recent urine specimen was loaded with PMNs and cultures grew an extremely resistant ESBL (Extended Spectrum Beta-Lactamase producing) E. coli. Resistant aerobic Gram negative rods- these organisms are becoming more prevalent over the last ten years with the overuse of antibiotics and the institutionalization of elderly Americans, These institutions (nursing homes and the like) are breeding grounds for ESBLs (most common are TEM, SHV, and CTX-M types) and KPCs. ESBLs are enzymes that confer resistance to most beta-lactam antibiotics. Beta-lactamases are enzymes produced by bacteria that open the beta-lactam ring preventing the antibiotic from properly performing its job. Multiple risk factors for ESBL, including indwelling catheters, longer length of stay, hemodialysis, ventilator assistance, and residency in a long-term care facility. The best proven therapeutic options of ESBL infections have been shown to be the carbapenem family. ESBLs were first described in 1960s in Greece. KPCs (Klebsiella pneumoniae carbapenamases) were first described in 1996 in North Carolina and are a special type of beta-lactamase. They are now worldwide. AmpC Beta-Lactamases are clinically important cephalo-sporinases encoded on the chromosomes of many of the Enterobacteriaceae and a few other organisms, where they mediate resistance to cephalothin, cefazolin, cefoxitin, most penicillins, and beta-lactamase inhibitor-beta-lactam combinations. In many bacteria, overexpression confers resistance to broad-spectrum cephalosporins including cefotaxime, ceftazidime, and ceftriaxone and is a problem especially in infections due to Enterobacter aerogenes and Enterobacter cloacae. Shy away from cephalosporins. 27. What is true of coagulase positive staphylococcus and coagulase negative staphylococcus? a. CONS is never pathogenic b. Staph aureus is always coagulase positive c. CONS includes Staph epidermidis d. A & B are correct e. B & C are correct f. All the above are correct 28. Which bacteria most commonly infects pregnant women, newborns, and alcoholics with chronic liver disease? a. Erysipelothrix rhusiopathia b. Legionella pneumophila c. Bacillus anthracis d. Listeria monocytogenes e. Neisseria meningitidis 29. Which of the following is not an aerobic gram negative diplococci? a. Neisseria gonorrhea b. Moraxella catarrhalis c. Haemophilus influenza d. Kingella e. Acinetobacter 30. Which of the following is the most common aerobic GNB that causes cystitis? a. Proteus b. E. coli c. Enterococcus d. Enterobacter e. Klebsiella oxytoca 31. What is the Gram negative bacillus associated with human bites? a. Peptostreptococcus b. Propionibacterium acnes c. Gemella morbilloram d. Eikenella corrodens e. Pseudomonas aerginosa 32. What is Lemierre’s Syndrome? a. Infected cavernous sinus thrombosis b. Septic jugular vein thrombophlebitis c. Pneumonia caused by an organism discovered after an outbreak at an American Legion convention d. Chronic maxillary sinusitis 33. What bacteria is associated with “acute chest syndrome” in patients with Sickle Cell crisis? a. Chlamydiophila b. Mycoplasma c. Hanta virus d. Staph aureus (MSSA) e. MRSA 34. What is the most common pathogen colonized in the colon? a. Clostridium difficile b. Escherichia coli c. Proteus mirabilis d. Bacteroides fragilis e. Citrobacter 35. Which of the following is not a gram negative bacilli? a. Bacteroides fragilis b. Clostridium gangrene c. Escherichia coli d. Klebsiella e. Enterobacter 36. Which of the following is not in the differential if a gram stain of a sputum is reported as GPC? a. Streptococcus pneumonia b. Staphylococcus aureus c. Enterococcus d. Moraxella catarrhalis 37. What is the most common vector for Rickettsial disease spread in the US? a. Surgical instruments b. Tick-borne c. Animal bites d. Unpasteurized goat cheese 38. Which disease below is not caused by a Bartonella species? a. Cat scratch fever b. Trench fever c. Bacillary angiomatosis d. Undulating fever e. Oroya fever (Carrion’s disease) 39. What is true of the spirochetes? a. Will not be seen on gram stain b. Treponema pallidum causes lyme disease c. Treatment for lyme disease is doxycycline d. They are screwed shaped e. A, B, and C f. B, C, and D g. A, C, and D h. All of the above are true of the spirochetes 40. Which of the following is not true of Pasteurella multocida (choose all that apply)? a. Causes cat scratch fever b. Zoonotic infection caused by cat bites c. It is a gram negative bacillus d. Exposure occurs through unpasteurized milk products e. A and D 41. Which of the following is not a fungus? a. Sporotrichosis b. Histoplasma c. Cryptococcus d. Candida albicans e. Mycoplasma 42. Which of the following bacteria below are acid fast bacilli? a. Legionella b. Chlamydia c. Mycoplasma d Mycobacteria e all of the above are AFB 43. Which organism is the smallest free living microorganism at 0.2-0.7 microns? a. Influenza b. Neisseria c. Mycoplasma d. Micrococcus e. Chlamydia 44. Which bacteria will you never see on a gram stain because it is obligate intracellular? a. Chlamydia trachomatis b. Clostridium perfringens c. Neiserria meningitidis d. Nocardia 45. What is the best treatment for ESBLs? a. Zosyn b. Aztreonam c. Linezolid d. Carbapenems e. Ciprofloxacin Answer Key: 27. E 28. D 29. C 30. B 31. D 32. B 33. A 34. D 35. B 36. D 37. B 38. D 39. G 40. B 41. E 42. D 43. C 44. A 45. D Cardiovascular Infections Case 41 A 50 year old male presents with a 3 month history of intermittent fevers, malaise and chills. He has a history of gum disease (pyorrhea) and recurrent dental work and molar extractions. Blood cultures obtained are positive for Strep viridans. Clinically, he has a new heart murmur, ECHO confirms mitral valve vegetations, and a dx of SBE (subacute bacterial endocarditis) is made. Dental procedures are still a prominent risk factor for SBE. Recent AHA guidelines have changed and are not recommending antibiotic prophyllaxis for most patients. Bacterial Endocarditis- infection of a valve or endovascular surface of the heart. Three types: Acute presents in 3 months. Five major pathogen groups- a) oral alpha streptococci (Streptococcus viridians) or enterococci b) Staphylococcus aureus c) coagulase- negative staphylococci d) aerobic gram negative rods e) candida. Pathogenesis- 1) valve destruction-CHF, heart block. 2) distant metastatic infection from bacteremia with septic emboli to any organ. 3) immune complex disease-- kidneys, Osler’s nodes. Diagnosis- use Duke’s criteria (new murmur; + blood cxs). Positive blood cultures must be sterilized. Treatment- high dose bactericidal antibiotics for 4-6 weeks. Prosthetic valve disease-usually removal of valve. Dental prophyllaxis- generally for congenital heart disease or prosthetic valves. Use amoxicillin 2 grams one hour before procedure. TEE is definitive for diagnosis. TTE misses up to 30% of vegetations. The following picture shows classic Osler’s nodes on the 5th left toe. Septic emboli in endocarditis are only seen in 15-20% of cases. They include splinter/conjunctival hemorrhages, Janeway lesions, and Osler’s nodes. Indications for surgery- CHF, emboli, heart block, perivalvular abscess, and large vegetations>1 cm. Cultures are negative in endocarditis for three major reasons: a) Previous administration of antimicrobial agents b) Inadequate microbiological techniques c) Infection with highly fastidious bacteria or nonbacterial pathogens (eg, fungi) Possible etiologies-The HACEK organisms (Haemophilus aphrophilus Actinobacillus actinomycete, Cardiobacterium hominis; Eikenella corrodens; and Kingella kingae) and Brucella were traditionally thought to be the most common agents of culture-negative endocarditis. An etiologic agent was identified in 275 patients (79 percent) and included: C. burnetii in 167 cases (48 percent), Bartonella spp in 99 cases (28 percent), Streptococci in 4 cases, Tropheryma whipplei in 2 cases, Abiotrophia elegans in 1 case, Mycoplasma hominis in 1 case, Legionella pneumophila in 1 case, Escherichia coli in 1 case. Diagnosis: PCR for Coxsiella, Bartonella can be helpful. Rx- Unasyn/Gent until serologies are back. American Dental Association current guidelines state that the use of antibiotics to prevent endocarditis before certain dental procedures is reasonable for patients with: prosthetic cardiac valve or prosthetic material used for cardiac valve repair a history of infective endocarditis a cardiac transplant that develops cardiac valvulopathy the following congenital (present from birth) heart disease. unrepaired cyanotic congenital heart disease, including palliative shunts and conduits a completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first six months after the procedure any repaired congenital heart defect with residual defect at the site or adjacent to the site of a prosthetic patch or a prosthetic device (that inhibit endothelialization) Except for the conditions listed above, antibiotic prophylaxis is no longer recommended for any other form of congenital heart disease. Case 42 A 32 year old electrician has been sick with a “flu-bug” since working in the United Arab Emirates on a special government job. He notes anterior chest pain with breathing, SOB, and there is a pericardial friction rub on physical exam. He has a large cardiac silhouette consistent with a “water bottle heart.” You suspect acute pericarditis. The EKG is as follows and shows global ST_T wave segment elevation. Pericarditis-patients often present with chest pain and fever. Pericardial rub- auscultated best with patient sitting forward. Watch for cardiac tamponade. Causes: 1) Viral most common. Including: Coxsackie B & A, enteroviruses, influenza, varicella. 2) Bacterial- contiguous spread from bacterial pneumonia. Hematogenous spread from staph, aerobic gm neg rods. 3) TB is rare. Rx- drain effusion (pericardiotomy with window), maybe pericardiectomy if loculated. IV antibiotics for 4 weeks. Rx of viral-consider NSAIDs, colchicine or steroids. Case 43 A 40 year old healthy male from Texas is in Chicago for the winter holiday visiting his grandmother. He catches a “bad flu” bug with associated achiness, high fever, congestion, and cough. Testing for Influenza A is positive. A few days later he develops severe SOB, PND, and orthopnea. Echocardiogram shows an EF of 19%. Five days later expires and autopsy shows severe Influenza Myocarditis. Myocarditis- viral etiology is the most common cause. Coxsackie B>A, enteroviruses, mumps, influenza, rubella, HSV, EBV, HIV, Hep. C, adenovirus, parvovirus, RSV. No infectious treatment. Look for arrythmias and cardiac failure. Bacterial causes- rarer, consider Lyme disease, rheumatic fever, diphtheria, staph, strep, TB, syphilis, GC, mycoplasma. Fungal- aspergillus and other dimorphic organisms. Protozoal disease-Chagas’ disease- common in South America, caused by Trypanosoma cruzi. Rx- benznidazole. Parasitic worm- Ascaris. Case 44 A 75 year old male developed sick sinus syndrome and had a pacemaker placed 3 weeks ago. Yesterday, he started with fevers, drainage from the pacemaker site, and tenderness. You diagnose a pacemaker site infection. The following picture shows the subtleness of redness and drainage from a pacer infection. Pacemaker infections- very low 1.6% rate. Perioperative contamination most common. Staph aureus (MSSA and MRSA) and Staph epidermidis account for 75% of infections. Staph bacteremia from distant site can seed generator pockets (look initially for fluid in the pocket) and lead systems. Endocarditis is a complication. Use TEE. Rx- removing the generator system and the lead is best. IV antibiotic 4 weeks. Difficult problem. Case 45 A 55 year old male has a CABG surgery 15 days ago. Yesterday, his sternal wound dehisced, and yellow, purulent drainage was cultured, growing MSSA. You diagnose a sternal wound infection, and mediastinitis. The following picture shows a patient after muscle flap procedure to repair his mediastinitis. Post-op Mediastinitis- along with empirical antibiotics, the patient was immediately taken to surgery, where the sternum and the mediastinal region was debrided and lavaged, and pectoralis muscle flaps were rotated into the area. The remainder of the hospital course was excellent, and the patient was discharged to home on IV antibiotics for 6 weeks. Usually monobacterial. 50% are gram- positive cocci (Staph). However, many organisms can cause it…gram negative bacilli, fungi, Legionella, Mycobacterium chelonae, M. fortuitum or Mycoplasma hominis. Surgical debridement is the mainstay of therapy. Devitalized tissues, bone wax, wires must be removed. Recurrent wound infection is lowest if a muscle or omental flap is used. Prior to cardiothoracic surgery, most cases of mediastinitis occurred from oropharyngeal infections (5% of Ludwig’s angina or epiglottitis) or a perforated esophagus. Harvest Site Infection (HSI)- a 62 year old female had a 3-vessel CABG surgery. Six days after surgery she presents with drainage and ulceration of the saphenous vein harvest site right leg. Debridement and IV antibiotics are needed. Case 46 T.J. is a 60 year old insurance executive with a history of a congenital bifid aortic valve. Because of stenosis, he had a cow prosthetic valve placed 6 months ago. He now presents with fevers, septic emboli to spleen (CT shows splenic infarct), and a cerebellar stroke. TEE shows a 3 cm vegetation on the aortic prosthesis, and blood cultures grow Staph epidermidis. Prosthetic valve endocarditis is diagnosed. Surgery is performed to replace the valve. Prosthetic Valve Endocarditis- majority of patients require surgery to replace infected valve. Early is < 8 weeks, Late is > 8 weeks after valve placement. Mortality for early disease is 70%, and 49% for late. Staph epidermidis is the most common organism, followed by Staph aureus and Strep. 46. In addition to the two major Duke Criteria (positive blood cultures and echocardiogram evidence of disease), which of the following are considered “minor” criteria in the diagnosis of endocarditis? A. Fever > 38°C B. Arterial emboli, pulmonary infarcts, conjunctival hemorrhages, Janeway lesions, or other vascular phenomena. C. Preexisting heart condition such as congestive heart failure, mitral valve prolapse, congenital malformation, or prior surgery. D. Intravenous drug use. E. Presence of Rh factor, Osler nodes, Roth spots, or other immunologic evidence. F. All of the above. 47. Infectious pericarditis is most commonly cause by which of the following “bugs?” A. Viruses: Influenza, Varicella, Coxsackie, etc. B. Bacteria: Staph, pneumo, Gram negative rods, etc. C. Tuberculosis D. Parasites E. Cardenella infectiosum 48. Bacterial causes of myocarditis are much less common than are viral etiologies. Which organisms should a clinician suspect if there is a diagnosis of myocarditis? A. Borrelia burgdorferi B. Corynebacterium diphtheria C. Mycobacterium tuberculosis D. Staphylococcus and Streptococcus species E. All of the above. 49. Pacemaker site infections are most often caused by perioperative contamination. With this in mind, which organisms are responsible for the majority of these infections? A. S. aureus and S. epidermidis B. S. viridans and Prevotella intermedia C. S. pneumonia and E. faecalis D. None of the above. 5. Mediastinitis is most often a complication of cardiac surgery and requires surgical intervention. What other conditions may cause mediastinitis? A. GERD B. Epiglottitis C. Boerhaave syndrome D. Mallory-Weiss tear E. A messy divorce F. B&C G. All of the above except E. Answers: 46. F 47. A 48. E 49. A 50. G Fever of Unknown Etiology (FUO) Introduction: Pathogenesis of fever, definitions of FUO Classic Definition of FUO- (FUO) was defined by Petersdorf and Beeson in 1961 as:Temperatures higher than 38.3 C or 101 F on several occasions, a duration of fever of more than 3 weeks, and failure to reach diagnosis despite 1 week of inpatient investigation. New Definition of FUO- in July, 2006, Durack and Street proposed a new system for classification of FUO:1) Classic FUO 2) Nosocomial FUO 3) Neutropenic FUO and 4) FUO associated with HIV infection Classification of Disease Categories- Major disease categories- Infection, Malignancies, and Non-infectious Inflammatory Diseases (NIID). Minor disease categories- Drug related fever (and NMS). Key: Always associate a FUO with a unique historical finding, unique laboratory finding, or a unique x-ray finding. This will make it easier to figure it out! Case 47 A 50 year old immigrant from India presents to you with a fever of unknown origin. He has had temps over 101 off and on for 3 weeks. You do a westergren sedimentation rate in the office and it is 112 (normals 5-15). You know something is seriously wrong. Further work-up reveals that he has extrapulmonary TB. High Westergren Sedimentation Rate- the erythrocyte sedimentation rate (ESR), also called a sedimentation rate, sed rate or Biernacki Reaction, is a nonspecific measure of inflammation that is commonly used as a medical screening test. Other APR (acute phase reactants) include CRP, ferritin, platelet count, fibrinogen, to name a few. CRP is frequently used with ESR. It elevates faster than ESR and goes down faster. ESR around or > 100 (often associated with FUO)- Differential diagnosis is: 1) occult abscess 2) endocarditis 3) occult cancer 4) occult tuberculosis 5) collagen-vascular disease- i.e. vasculitis (Wegener’s, PMR, etc.) or 6) osteomyelitis/septic joint. Case 48 A 67 year old female presents to you with fevers off and on for 4 months. All of her blood work is normal (except a sed rate of 95) and cultures are negative. Urinalysis shows 5-10 RBCs/HPF. You recommend a CT of the abdomen. CT shows a large mass in the kidney consistent with a hypernephroma or renal cell Cancer. Fever in the setting of cancer- found in GI solid tumors, especially with liver metastases. Atrial myxomas, Renal cell cancer, Lymphomas (Pell-Ebstein fever), pheochromocytoma are also all associated with fever. Case 49 A 45 y/o insurance broker presents with a 2 month history of night sweats and intermittent low grade fevers. All of his blood tests are normal except his LFTs. LFTs show that the alkaline phosphatase is very elevated to 300, suggesting a ductal obstruction. CT shows hepatomegaly and liver biopsy is performed showing non-caseating (caseation means “cheese-like” granulomas. Sarcoidosis is finally diagnosed. Fever in the setting of granulomatous disease-granulomatous diseases including- sarcoidosis, fungal (non-caseating) diseases like histoplasmosis, blastomycosis, or toxoplasmosis, granulomatous hepatitis, Wegener’s disease, and the caseating diseases of TB, or MAI. Case 50 An 70 year old woman presents with right-sided temporal headaches, right-sided blurry vision, and fevers off and on for 3 weeks. You suspect temporal arteritis (a collagen vascular disease) and recommend a stat biopsy and prompt oral steroid treatment. Fever in the setting of collagen vascular disease- such as SLE, temporal arteritis, polyarteritis nodosa, or autoimmune hepatitis. These patients frequently have high sed rates (ESR) of 80 to 110, and CRP >50, and low complement levels. Case 51 A 60 year old female presents to the ER with fevers to 104, muscle cramping, tremor, and hypertension. Symptoms have been going on for a week since she was started on Reglan. Her CPK is 16,000 and she has a metabolic acidosis. You diagnose Malignant Neuroleptic Syndrome secondary to metoclopramide. Fever in the setting of medications affects- drug fever (anti-convulsants like dilantin, tri-cyclics like amitriptyline, antibiotics like beta-lactams), or Malignant Neuroleptic Syndrome- related to use of anti-psychotic drugs, or Reglan. Look for delirium, fever, autonomic instability with profound diaphoresis, high CPK, muscle rigidity/cramps and tremor. High BP and metabolic acidosis are the rule. Looks like acute PD (Parkinson’s Disease) related to D2 dopamine receptor blockade. Treat with Dantrolene, bromocriptine, and valium. Case 52 A 60 year old car salesman presents with fevers off and on for 6 weeks. He notes being “flushed” and sweating a lot at work which is embarrassing to him. His blood pressure in the office is 210/120 and you suspect a pheochromocytoma. Pheochromocytoma- can be diagnosed by CT of the abdomen and a 24 hour urine for VMA/metanephrines with serum catecholamines Fever in the setting of endocrine problems- hyperthyroidism (especially in viral thyroiditis-subacute), pheochromocytoma (tumor of the adrenal medulla). Case 53 A 78 year old female living at home alone fell in her bathtub injuring her pelvis. X-rays show non-displaced fractures of the iliac crest. She is hospitalized for pain control. You note persistent low grade fever and anemia. Pelvic fractures are noted to bleed with the potential to cause large hematomas. Fever in the setting of blood clots and hematomas- pulmonary emboli-CP with SOB, tachycardia, or occult hematoma- from pelvis fractures, CNS strokes (“central fever”), or intra-abdominal-related to trauma. Case 54 A 50 year old hunter presents to your office in the summer with 4 weeks of malaise, flu-like symptoms, myalgias, skin rash, fevers, and headaches. He is generally healthy previous to this syndrome. Blood work shows leukopenia, thrombocytopenia, and increase in ALT to 200 with a CPK of 1000. He did have a tick bite while hunting about one month ago. You suspect rhabdomylosis and Ehrlichiosis or Lyme’s disease. A serum PCR test confirms the diagnosis of Ehrlichiosis. The following schematic shows the lifecycle of Human Granulocytic Ehrlichiosis. FUO in the setting of high CPK, Rhabdomyolysis/Myositis- Differential diagnosis: Pyogenic- Staph and Beta-Strep infections, Aeromonas, Clostridia. Nonpyogenic- Leptospira, Mycoplasma, Legionella, Viral causes- influenza A and B, EBV, Coxsackie virus, HIV, Dengue, and Adeno. Tickborne infections are prominent – think about Ehrlichia, Babesiosis, Lyme’s, and Rocky Mountain Spotted Fever. Parasites- Toxo, trichinella, Taenia solium, Sarcosystis. Fever in the setting of joint pains (polyarthralgias)- Viral- parvovirus B19 (erythema virus), Hepatitis A,B,C, HIV, Rubella, HSV, CMV, Mumps, HTLV-, Chickengunya. Lyme disease. RA. PMR. SLE. Whipples. Fungal infections. Case 55 A 64 year old retired factory worker presents with low grade fevers off and on for 4 weeks associated with upper anterior neck swelling and pain. She has not seen a dentist for over 5 years because of a lack of dental insurance. Panorex x- rays show a right lower molar abscess. She will likely need a root canal or tooth extraction. The following picture shows this process; also called Ludwig’s angina. Fever in the setting of ENT/dental infection- occult sinusitis/dental infection. Generally poor dentition or gum disease. Ludwigs is an infection involving the submental, submandibular, or sublungal spaces. It can be bilateral. Case 56 A 14 year old boy recently returned from his first deer hunting trip to the Eau Claire, Wisconsin area. He had multiple arthropod tick bites during the trip. He presents to you with flu- like symptoms of 1 week duration and a new skin rash consistent with erythema chronica migrans, associated with myalgias. You suspect Lyme’s Disease. Fever in the setting of arthropod bites- Causes- human monocytic ehrlichiosis (E. chaffeensis), Lyme’s disease-caused by Borrelia borgdorferi, Rocky Mountain Spotted Fever- caused by Rickettsia rickettsii, Anaplasma- caused by Human Granulocytic Anaplasmosis, a rickettsial parasite spread by deer ticks inducing hemolytic anemia. Babesiosis-malaria-like parasite disease also spread by Ixodes scapularis (same tick that vectors Lymes/ Ehlichiosis), Rx with quinine and clindamycin. Lyme’s Disease-there are 3 stages described in Lyme infections: early localized, early disseminated, and late. The early localized stage of the infection manifests with a nontoxic, nonspecific febrile illness and the classic ECM (Erythema Chronica Migrans) lesion(s) described as a red patch with central pallor. No immunity in Lymes. The following picture shows classic ECM. Case 57 A 62 year old short term traveling missionary presents to you with a fever of 2 weeks duration since getting back from Peru, where he was exposed to multiple mosquito bites. He did not take malaria prophylaxis because he was told by his PMD that he did not need it. You order a thin and thick blood smears on labs, and the pathologist diagnoses Plasmodium vivax. A 50 year old ICU nurse went on a 3 week medical missionary trip to India. Two days before leaving, she developed fevers to 104 degrees, malaise, joint pains and muscle pains, headache, and a rash on her trunk. She sees you a week later in the travel clinic with persistent arthralgias. You suspect Chikungunya. Chikungunya is an alpha virus spread by the Aedes mosquito in Africa, India, and Southeast Asia. There is no treatment and no vaccine. It looks like Dengue Fever clinically. Dx by serology (PCR). Persistent arthralgia can be severe for weeks, months, or years. Fever in the setting of international travel- look for Entamoeba histolytica or malaria (Plasmodium falciparum is by far the most lethal of the Plasmodium species), and other parasitic infections (check for high eosinophils if worms present- see Parasite section), dengue or leishmaniasis (sandfly vector) pending location of travel. Case 58 A 55 year old farmer presents to you with a 4 month history of diarrhea, weight loss, joint pains, confusion and intermittent fevers. He is up-to-date on colonoscopy 9 months ago, which was normal. Stool for O&P, and routine bacterial pathogens is normal. CT of the abdomen and pelvis is normal. You suspect Whipple’s disease. How would you diagnose it? Fever in the presence of abdominal pain, diarrhea- malabsorption syndrome, neurological symptoms, joint pains with negative pathogen stool work-up- think of Whipple’s Disease (Tropherhyma whipplei- in the Actinomycetes family); treated with 1 year of doxycycline, amoxicillin, or sulfa). Also, think about IBD (either Crohn’s disease or ulcerative colitis), occult abscess or bowel ischemia in patients with diarrhea and fever, guiac positive stool with negative stool work- up. Case 59 A 40 year old horticulturist and DNR worker presents to you with sore throat, jaundice, malaise, and fevers to 100.5 off and on for the last 3 weeks. Direct bilirubin is 6.5 and the ALT is 400. She normally a health individual. What is the differential diagnosis of jaundice, increased LFTs (transaminitis) and fever? FUO- jaundice and high LFTs- Differential diagnosis:Viral diseases- EBV (mono), CMV, Hepatitis A,B,C,D,E,G, Ebola, Yellow fever, Dengue. Parasitic- malaria, Entamoeba histolytica, Toxoplasmosis, Babeosis, Cryptosporidiosis, Ascariasis (roundworm). Bacterial- leptospirosis (Weil’s disease), overwhelming sepsis- i.e. staph or strep, Borrelia (Relapsing Fever) Granulomatous hepatitis from syphilis, toxo, fungal, or TB like organisms. Our patient had a positive IgM CMV serology titer. Leptospirosis- a spirochetal disease causing “infectious jaundice”. Weil first described it in 1886. It caused epidemics among Native American Indians in the 1600’s. Napolean’s army suffered severely from it. It affected Civil War and World War I troops. Modern day epidemics occur in Nepal. Risk factors are many; crewing is one. Doxycycline prevents it for travelers. The following schematic shows the lifecycle of Leptospirosis. Case 60 A 24 year old Peace Corp worker in Ethiopia comes home because of malaise and persistent relapsing fevers over the last 6 weeks. She has been living a rural village where she has been exposed to lice and tick bites. Her CBC reveals a hemaglobin of 8.6 gms%. Work-up for hemolysis is + and shows high LDH, high retic count, and a + Coomb’s test. You suspect Borrelia recurrentis (Relapsing Fever). Infectious causes of hemolytic anemia- Bacterial- sepsis due to staphylococci, streptococci, pneumococci, meningococci. Bacterial endocarditis. Salmonella infections. Escherichia coli 0157 gastroenteritis (hemolytic uremic syndrome). Borrelia recurrentis (Relapsing Fever)- caused by tick bite or contact with body lice. Leptospirosis (Weil’s disease). Mycoplasma (immune hemolysis/+ cold agglutinins). Viral- Infectious mononucleosis (immune hemolysis). Protozoan- Malaria. Babesiosis-“Malaria of the Northeast U.S.” African trypanosomiasis. Toxoplasmosis. Leishmaniasis. Case 61 You are asked to see a 50 year old post-op CABG patient who has a FUO. He has been in the ICU for 8 days post-operatively with complications of GI bleeding, delerium, and pulmonary infiltrates. What is the differential diagnosis of FUO in the ICU? FUO in the setting of ICU- Causes-Nosocomial infection- pulmonary, urine, surgical wound, central line infection. Pulmonary emboli. Atelectasis. Sinusitis/OM from mechanical ventilating. Drug fever- i.e. seizure meds, or MNS (Malignant Neuroleptic Syndrome). “Central fever”-stroke or CNS bleed. Phlebitis. Post-op ischemia. Occult Gallbladder disease. Case 62 A previously healthy 50 year old RN presents to you with a fever of unknown origin for the last 4 weeks with temps greater than 100.5 on and off. She had an uneventful laparoscopic cholecystectomy 6 weeks ago for cholecystitis and gallstones. In the face of a FUO, the CT scan of the abdomen is ordered and shows a liver abscess. An 8 year old child presents with flu like symptoms of 2 ½ weeks duration, associated with sore throat, conjunctivitis, joint pains, swelling of the hands and feet, a strawberry tongue, a macular rash, cracked lips, and cervical lymphadenopathy. Platelet count is over 1,000,000. You diagnose Kawasaki’s Disease, an autoimmune vasculitis syndrome. Kawasaki’s Disease- unknown cause. Described in 1961.Thought to be autoimmune. Associated with adenovirus. Systemic vasculitis occurs with coronary arteritis, aneurysms. Treatment with IVIG, steroids, and sometimes biologics. Fever in the setting of “rarer” infections- deep infection (abscesses- spleen,liver,psoas), Mycobacterial disease (TB, MAI), occult fungal diseases (Blastomycosis can look like lung cancer), occult pyelonephritis, parasitic infections (look for eosinophilia if worms present), viral infections (look for leukopenia and right shift in WBCs-lymphocytosis), HIV, vasculitis. Work-up of FUO- Take a thorough history. Check: CBC, CMP, U/A, Sed rate, CRP, CPK, ANA, TFTs, serum cortisol, serum catecholamines, d-dimer, HIV, check for occult dental/sinus disease, blood cultures, thin/thick blood smears if international travel to developing countries, Lyme’s antibody, serum PCR for ehrlichiosis. PCR for Tropherhyma whippli if diarrhea present. Review medication profile. Consider chest X-ray, CT abdomen/pelvis, echocardiogram, Indium/ gallium scan. Check travel history-consider stools for O & P, bacterial stool culture. 51. Which of the following statements is not TRUE of extrapulmonary tuberculosis? A. Extrapulmonary locations are reactivation sites; the primary infection occurred earlier. B. The pathology of extrapulmonary lesions is very different from pulmonary lesions. C. Patients with extrapulmonary TB often do not have a cough. D. Lymph nodes comprise almost 30% of the cases of extrapulmonary TB. 52. Fever of unknown origin in a person over age 50 should prompt investigation for what problem? A. Occult CA. B. Hepatitis C. Blood clot D. PE E. All of the above. 53. Which of the following diseases may cause granulomas of the liver? A. Sarcoidosis B. TB C. Histoplasmosis D. Blastomycosis E. All of the above 54. Which combination of laboratory values and symptoms would you expect in a patient with temporal arteritis? A. Fever, blurred vision, headache, ?ESR, ?CRP B. Headache, blurred vision, joint pain, ?ESR, no rise in CRP C. Fever, blurred vision, headache, ?ESR, ? CRP D. Headache, blurred vision, fever, no rise in ESR or CRP 55. Malignant Neuroleptic Syndrome may be caused by which of these drugs? A. Bromocriptine B. Dantrolene C. Valium D. Reglan E. Tylenol 56. Pheochromocytoma classically presents with what symptoms/signs? A. Fever B. Hypertension C. Flushing D. All of the above 57. Which of the following statements is FALSE about a hematoma? A. It may cause fever in an otherwise-healthy patient. B. Bleeding from a pelvic fracture is usually secondary to damage to the pelvis venous plexus. C. Leukocytosis caused by large hematomas is treated with empiric antibiotics. D. Large volume blood loss may mimic the symptoms of sepsis. 58. How is Ehrlichosis differentiated from Lyme Disease? A. Human Monocytic Ehrlichosis produces fever; Lyme does only rarely. B. Lyme produces fever; Ehrlichosis does not. C. Serum PCR tests for HME; ELISA and Western Blot for Lyme. D. Morulae (Ehrlichia inclusion bodies) are present on buffy coat examination in patients with HME. 59. Which of the following signs/symptoms is often present in a patient with Ludwig’s angina? A. Chest pain and DOE B. Bilateral mouth pain/swelling C. Peripheral edema and pronounced ecchymosis D. Visual impairment 60. Ixodes scapularis is a vector for all of the following human diseases EXCEPT: A. Babesiosis B. Hanta virus C. Anaplasma D. Lyme Disease 61. Which of the following statements is FALSE about pyogenic liver abscesses? A. They carry a very high mortality rate. B. Often, they are cryptogenic. C. The most common causes are cholecystitis, trauma, and portal vein infection from the GI tract. D. They are treated with percutaneous drainage and antibiotics. 62. Which Malaria-causing organism is known to cause most morbidity and mortality from the disease? A. P. ovale B. P. malariae C. P. knowlesi D. P. falciparum E. P. vivax 63. The biggest hurdle to overcome in diagnosing Whipple’s Disease is what? A. Getting an adequate specimen. B. Laboratory error. C. Patient noncompliance. D. Adding it to the differential diagnosis. 64. Which of the following statements are true of Leptospirosis? A. It is prevented by taking antibiotics. B. Risk factors include vigorous outdoor activities in areas with infected wildlife. C. Fever and jaundice are major signs. D. All of the above. 65. Which of the following is an infectious cause of hemolytic anemia? A. Salmonella B. Malaria C. Relapsing Fever D. Mononucleosis E. All of the above Answers: 51. C 52. E 53. E 54. A 55. D 56. D 57. C 58. C 59. B 60. B 61. A 62. D 63. D 64. D 65. E Fungal Infections Introduction- Anti-fungal Drugs (5 classes)- Imidazoles- work in cytoplasm. Drug interactions- binds the liver CYP450 system. Fluconazole- active against most Candida species other than C. krusei. Use fluconazole IV at 6mg/kg/day. Torulopsis glabrata has increasing resistance ~20%. ltraconazole (Sporanox)- use for histoplasmosis, blastomycosis, sporotrichosis, Aspergillus. Voriconazole- 96% bioavailability, use for T. glabrata, C. krusei, Aspergillus -4mg/kg q 12 hrs IV, then 200 mg po BID. Posaconazole, isavuconazonium in 2015- po or iv). Echinocandins- acts on cell wall synthesis. Only IV. Cidal-like amphotericin. Good for azole-resistant Candida, Aspergillosis. Caspofungin, mycafungin, anidulafungin. Poor urinary concentration. Polyenes- Nystatin or Amphotericin B- cell membrane inhibitor-.5 mg/kg/day. Toxicities-rigors, phlebitis, bone marrow suppression, renal/hepatic impair, electrolyte imbalance. Lipophilic Ampho B- decreases toxicity. 5mg/kg/day. Very expensive. Terbinafine- allylamine, blocks membrane synthesis. Used for skin and nail disease. 5-Flucytosine- inhibits DNA, use 37.5 mg/kg/dose QID. OK for fungal UTIs or synergy with other agents like Ampho B. Case 63 A 39 year old male presents to your office with a 6 month history of a rash on his face which is not responsive to OTC meds. Through careful history, you find that he is at increased risk for HIV infection. HIV Elisa testing comes back positive, and the western blot confirms the diagnosis of HIV. You suspect seborrheic dermatitis. Dermatophyte infections- caused by Trichophyton, Microsporum, Epidermophyton. Papulosquamous rash, usually pruritic. Also called “ringworm”. Tinea pedis-athlete’s foot, scaling between toes (especially 4th and 5th), Tinea manuum -palms of hands affected. Tinea capitis- scalp. Tinea cruris – groin folds Tinea corporis- body involved, Tinea versicolor- caused by Malassezia. Rx topical imidazoles or weekly fluconazole orally. Seborrheic dermatitis-caused by dermatophytes-Rx with 2% Nizoral shampoo, topical steroids. Case 64 A 50 year old CEO comes into the office with thickened yellow toe nails and he is embarrassed to go to the beach because of the problem. You diagnose onychomycosis and recommend treatment. Remember that removing the nails doesn’t cure onychomycosis. Onychomycosis- difficult to treat, 30-50% recurrence. Thickened yellowed/ darkened nails. Differential: dermatophyte, psoriasis, PVD, lichen planus. Fungus lives in nail bed. Removing nail doesn’t cure. Use po Terbinafine 250 mg daily 6-12 weeks. Fluconazole weekly x 6 months. Itraconazole also used in accelerated regimen. Laser has been used of late with success. Case 65 A 33 year old patient with HIV infection presents to the office with a sore throat and whitish plaques. You diagnose thrush, an oral form of candida albicans and recommend treatment. Candida infections- most commonly C. albicans (60%), Torulopsis glabrata (15%). Also C. parapsilosis (15%), C. tropicalis, C. krusei, C. lusitaniae (Ampho. B resistant). Thrush- increases with steroid use, DM. Rx- Nystatin swish and swallow or Mycelex Troches qid x 10 days. Esophagitis- fluconazole 200 mg (itraconazole also) for 7-14 days, Vaginitis- associated with pregnancy, diabetes, antibiotic use. Intense pruritis, “curd-like” discharge. Rx- topical azole creams or fluconazole. Candida UTls- increased in diabetics, if hardware, stones, abnormal anatomy then hard to treat. Rule out colonization. Use fluconazole 7- 14 days or lipophilic Amphotericin B.3mg/kg X 1 dose. Remove Foley catheter ASAP. Invasive candidiasis-1,3)-β-D-glucan(BG) is a biomarker for invasive candidiasis (IC). BG is a major cell wall component of most fungi. A decrease in BG levels was associated with response to antifungal therapy. An increase in BG levels correlates with treatment failure. An initial BG level of posaconazole, > the echinocandins. Case 68 A 46 year old newly diagnosed patient with HIV and a CD4 count of 100 and viral load of 80,000 presents with fevers, malaise, stiff neck, photophobia, and confusion. Spinal tap shows a cell count of 1000 with a right shift, India ink is positive for Cryptococcus neoformans, and Cryptococcal Antigen is positive at 1:32. The following India ink stain shows the white “owls eyes” of Cryptococcus. Cryptococcosis- this dimorphic fungus is more common in AIDs and lymphoma patients. It causes meningitis with positive India ink and positive antigen, cavitation in lung, granulomas in liver, as well as skin disease. Fluconazole and 5-FC- treatment of choice and decent CNS penetration. Case 69 A 45 year old male DNR worker presents with a chronic pneumonia. He has had no response to antibiotic treatment and continues with chills, fevers, cough, and SOB. Blastomycosis is diagnosed. The following histology stain shows the classic budding yeast of Blastomycosis. Blastomycosis- once known as “Chicago’s disease”, discovered late 1800’s. Seen from Minnesota to Mississippi to West Virginia. “Budding yeast” seen on histology. Can look like lung cancer. Invades bone, liver, skin, prostate, CNS. Can cause sepsis. Rx- itraconazole p.o. bid for several months. Diagnose with tissue bx. Bronchoscopy can miss the dx. Case 70 A 52 year old postal worker presents with a FUO for 6 weeks. His only abnormality is high LFTs with an alkaline phosphatase of 400 and ALT of 150. CT scan of the liver is consistent with granulomatis hepatitis. Liver biopsy grows Histoplasma capsulatum. Histoplasmosis- more common in Indiana, Ohio, Kentucky, central Illinois. Clinically similar to Blastomycos

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