A PGY-1 GUIDE TO INFECTIOUS DISEASE AND SEPSIS

1. A PGY-1 GUIDE TO INFECTIOUS DISEASE AND SEPSIS JAY SELLERS AND CHRIS MILLER

2. COMMON BACTERIA WE ENCOUNTER IN THE HOSPITAL • GRAM POSITIVES • Staph • Strep • Clostridium • GRAM NEGATIVES • Neiserria • E. coli • Klebsiella • Pseudamonas

3. STAPHYLOCOCCOUS • Gram Stain: Gram-Positive Cocci in Clusters • Staph aureus • MSSA • CA-MRSA • HA-MRSA • Staph epidermidis

4. Staph aureus (SA) • Coagulase Positive • Community-Acquired MRSA (CA-MRSA) • Cellulitis (“a bug/spider bit me doc!”) • Severe invasive infections (endocarditis, cavitary pneumonia, epidural abscess, endopthalmitis) • Hospital-Acquired MRSA (HA-MRSA) • Line infections • Pneumonia, especially VAP or in patients w/chronic lung dz • Endocarditis

5. Antibiotics vs. Staph aureus • CA-MRSA • PO options: Bactrim, doxycycline, clindamycin, linezolid • More serious infection: vancomycin, daptomycin, linezolid, tigecycline • HA-MRSA • Vancomycin, daptomycin, linezolid, tigecycline • At Jeff, we use dapto or linezolid for MIC>=2 (consider this “VRSA” • MSSA- all of the above, but is oxacillin/nafcillin/methacillin susceptible • “Give penicillin to your mother if she gets MSSA. Give your mother-in-law vanco.” -Joe Desimone

6. Staph epidermidis (coagulase negative staph or “CNS”) • Usually a contaminant from the skin seen on an isolated positive blood culture • Can cause pathology in patients with indwelling metal hardware (cardiac valves, artificial joints, pacers, Baclofen pumps) • Antibiotics: can be resistant to methacillin, usually start with vanco and await sensitivities

7. Streptococcus • Gram positive cocci in chains • Beta-hemolytic strep (heavy hemolysis- TOXIC) • Group A (Strep pyogenes, GABHS) • Group B (GBS) • Group C • Alpha-hemolytic strep (medium hemolysis) • Viridans group strep • Strep pneumo • Gamma-hemolytic strep (no hemolysis) • Group D (Enterococcus) • Strep bovis

8. Beta-hemolytic Strep • Group A Strep- Strep pyogenes • “Strep throat” • Pyotoxic infections- necrotizing fasciitis, toxic shock • Group B Strep (GBS) • Genito-urinary colonizer • Neonatal infections (think back to prenatal testing on OB/GYN)- pneumonia, meningitis • Elderly, immunocompromised • Group C Strep • Pyotoxic infections similar to GAS, less common

9. Alpha-hemolytic Strep • Viridans Strep • Head and neck infections (sinusitis, orbital cellulitis) • Endocarditis (associated with poor dentition) • Strep pneumo • Pneumonia • Meningitis • Otitis media

10. Gamma-hemolytic Strep (non) • Enterococcus • Genitourinary infections • Strep bovis • Typical test question: Strep bovis bacteremia/endocarditis, think colon cancer

11. Antibiotics vs. Strep • Most strep are not very resistant, can usually treat empirically with a beta-lactam up front • Ex: ceftriaxone for CAP, amoxiciilin for strep throat or otitis • Exceptions • Meningitis, endocarditis • Enterococcus- often one of the MDRO (multi-drug resistant organisms)

12. Antibiotics vs. Enterococcus • Generally susceptible to same antibiotics that work vs MRSA (vancomycin, daptomycin, linezolid), usually Bactrim, cipro if infection acquired in community • OFTEN see resistance to vancomycin now in hospital (“VRE”) • Cover patients with chronic or hospital-acquired infections with dapto or linezolid up front

13. Clostridium • C. difficile • Causes C.diff diarrhea • Classic characteristics: • patient on recent abx or hospitalized or hx IBD • Frequent diarrhea • Fevers • WBC>20 • Toxic megacolon (severe) • Antibiotics • Metronidazole (Flagyl) or PO vancomycin • New antibiotics emerging

14. Neiserria • Gram-negative diplococci • N. gonnorhoeae • Usually will see in clinic, STD causing infectious urethritis • PID • Dermatitis-arthritis • N. meningitidis • Meningitis- young patients living in close quarters (college students, army barracks) • Need prophylaxis for close contacts • Vaccine available • Antibiotics: usually ceftriaxone

15. E.coli/Klebsiella • Gram-negative rods • Lactose fermenting • Infections • UTI’s • Pneumonia • Gram-negative sepsis • Travelers Diarrhea, hemorrhagic diarrhea (O157:H7), HUS with E. coli

16. Antibiotics vs E.coli/Kleb • E.coli tends to be more susceptible and seen more in community (women with UTIs)- can use Bactrim, Cipro • Klebsiella generally more resistant • Most resistant strains in vented patients, nursing home patients, patients with bladder dysfunction, hospital “frequent flyers” • Extended-Spectrum Beta-Lactamase (ESBLs) • Knock out beta lactams, floroquinolones, late-generation cefalosporins, beta lactam/beta lactamase inhibitors (ampicillin-sulbactam, piperacillin-tazobactam) • Use carbapenems, aminoglycosides, tigecycline, colistin • Kleb pneumo Carbapenemase (KPCs) • Knock out all of the above, PLUS carbapenems, often one or more aminoglycosides • Can use tigecycline, sometimes an aminoglycoside, colistin • Sometimes PAN-RESISTANT

17. Pseudomonas aeruginosa • Gram-negative rod • Non-lactose fermenting • Infections • Hot tub cellulitis • Otitis externa, malignant otitis • Severe, hospital-acquired infections- UTIs, Pneumonia, sepsis

18. Antibiotics vs. Pseudomonas • Only PO option is Cipro (effective 50%-ish of the time) • Piperacillin (anti-pseudomonal penicillin) • Some 3rd, 4th generation cephalosporins (ceftazidime, cefepime) • Aminoglycosides • Carbapenems (except ertapenem) • Aztreonam (really only used to cover pseudamonas in penicillin-allergic pts) • Can frequently be resistant to several of the above- we often DOUBLE COVER if we have a high suspicion

19. Anaerobes • Gram positives, gram negatives • Can often produce a beta-lactamase, sometimes even ESBL • Infections • Head/neck • Aspiration pneumonia/pulmonary abscess (people with poor dentition) • “below-the-diaphram” infections • Antibiotics • Beta lactamase inhibitor combos: amox-clav (Augmentin), ticarcillin-clav (Timentin), amp-sulbactam (Unasyn), piperacillin-tazobactam (Zosyn) • Clindamycin • metronidazole

20. Atypicals • Usually concerned with these in pneumonia (or chlamydia in non-gonnococcal urethritis) • Chlamydia, mycoplasma • Legionella (pneumonia w/hyponatremia, diarrhea, sick patient) • Generally covered by floroquinolones, azithromycin

21. Steps to treating an infection • History/physical, differential • Source identification • Choose appropriate initial antibiotics to cover most serious pathogens that are associated • In hospital, MRSA and pseudomonas will generally kill someone the fastest • Check GRAM STAINS and cultures before abx IF POSSIBLE, multiple sources, multiple times • Check gram stain- narrow coverage if confident • Check culture- narrow again • Check susceptibilities- choose final agents

22. Pneumonia • CAP • Strep pneumo, H.flu, atypicals • In community, treat with respiratory floroquinolone (moxifloxacin, levofloxacin)- rising resistance to azithro • In hospital, treat with respfloroquinolone or ceftriaxone/azithro • HAP • Need to cover for MRSA and pseudamonas • Generally start with vanco + Zosyn • If patient is a “frequent flyer,” might sub carbapenem for Zosyn • VAP • Need to cover MRSA + worry about ESBLs/KPCs and pseudomonas • High mortality • Generally start vanc/Zosyn or vanc/carbapenem, sometimes will DOUBLE COVER with aminoglycoside • EXTUBATE PATIENT

23. Meningitis • Fevers, HA, ill-appearing, neck/back pain, normal mental status • Most common- strep pneumo • N. meningitidis- young patients, close living quarters- RASH • Listeria- gram-pos rod • Patients with impaired immunity, age >65 • Start with ceftriaxone + vancomycin • Small percent strep pneumo resistant to CTX, serious infection, this is why we add vanc • Give STEROIDS before abx if suspect strep pneumo • ADD ampicillin if at risk for Listeria

24. UTI • Avoid catheters- document Foley status in note EVERY DAY and ask “can I remove this” • PLEASE CHECK GRAM STAIN • If a GRAM POSITIVE shows up, probably going to be Enterococcus, can SIGNIFICANTLY narrow abx • Entercoccos, E.coli, Proteus, Kleb, Enterobacter • Simple: bactrim, nitrofurantoin, ciprox 3 days • Complicated: cover for appropriate bacteria depending on suspected level of resistance • In frequent/bladder dysfxn patients, may need to cover VRE (linezolid/dapto) and pseudomonas/ESBL (carbapenem)

25. Cellulitis • Most patients, cover MRSA and strep • Bactrim, doxy, clinda, vanc, linezolid, dapto • Diabetics/immunocompromised- also worry about anaerobes, pseudomonas • May need to ADD coverage for these • Necrotizing fasciitis- suspect in ill cellulitis pt, diabetics, patients with pressure ulcers, critically ill with no defined process • PALPATE cellulitic areas/wounds for subQ air • Check CPK • IMAGE for free air- CALL SURGERY IMMEDIATELY • ADD clindamycin- inhibits toxin production by strep • Cat bites- Pasteurella, use Augmentin or Unasyn

26. Sepsis • Hypotensive, tachycardic patients, likely infectious source, febrile • Examine vasodilated, “warm” • AGGRESSIVE volume resuscitation (2-3L NSS, wide open up front, may need INTUBATION if pulm edema) • Antibiotics targeted against likely pathogens (often cover MRSA/pseudomonas, often double cover) • These take TIME to work, the fluid is most important • Pressors- consider if hypotense after 2-3L or if pt hypoxic from fluid • Need central venous catheter for administration • Stress steroids- hydrocortisone 50mg IV q6hr • Consider in patient not responding to all of above or if patient has taken >10mg prednisone for any 3 wk over past yr • Activated Protein C- no longer used

27. Neutropenic Fever • May be only clinical sign infection • Patients with neutrophil fraction of total WBC (ANC) <1000 • MUST start abx in these patients when they have fever • MUST cover pseudomonas with a reliable agent (ceftaz, cefepime, piperacillin, aztreonam) • Cover MRSA if invasive lines, rash, high suspicion, or if fever dose not relapse on above treatment at 24-48hr • Cover fungus if high suspicion or no resolution/etiology in several days

28. Endocarditis • Suspect in patient with fevers, wt loss, poor dentition, IV drug use, previous IE or previous documented bacteremia, indwelling chronic lines • Often sustained bacteremia • If high suspicion, initial abx should cover MRSA/strep (usually vancomycin) • Need to combine vanc with gentamicin for SYNERGY for empiric initial coverage

29. Septic Arthritis • Can be associated with patients with gout flares • Must be tapped and sent for stain and culture • Differential is gout, pseudogout • Crystals will not be seen • Extremely high WBC, bacteria on gram stain • Often Staph • May need washout in OR by ortho

30. Fungemia • Immunocompromised patients, neutropenic patients, TPN, ill patients • Often yeast Candida albicans, can also see Candida glabrata and others • C.albicans usually sensitive to azoles (fluconazole) • C.glabrate and other hospital yeast often resistant to fluconazole, so start with eichinocandin (caspofungin, anidulofungin, etc) • Remove invasive lines, stop TPN

31. Influenza • Suspect in winter • Respiratory sx’s, cough, fevers, muscle aches, N/V • Tamiflu effective if given <48hr after symptom onset • If sick patient and high suspicion flu (like H1N1 outbreak), would probably try Tamiflu regardless of time after onset

32. Non-infectious fevers • Gout flare- patients getting HD or diuretics often • DVT/thrombosis • Central fever • NMS/malignant hyperthermia (suspect if T>103F) • Post-transfusion (even days) • Drug fever/allergy • cancer

33. Case 1 • 60yoF PMH CKD on HD via catheter, DM2, HTN. Recent hospitalization 1 month ago for bacteremia with coag-negative staph, had line change. Back in ED with fever to 102F. Also a cough/sputum, diffuse muscle aches. • Differential? • Potential pathogens? • Testing? • Initial therapy?

34. Case 2 • 57yoM, DM2, CKD, gout, here for initiation of HD. No previous access. Was extremely hypoxic on admission. On Day 3 admission, spikes fevers to 101F. Has diarrhea. Bilateral knee and shoulder pain. Normal WBC. • Differential? • Potential pathogens? • Testing? • Therapy?

35. Case 3 • 55yoM PMH DM2, HTN presents to ED because his wife “forced me.” “He’s not eating and he’s vomiting” she says. He admits nausea, vomiting, lethargy, fevers x3 days. He’s reclining on his side because “my butt hurts where they lanced a boil 5 yr ago.” He is tachycardic (sinus) to 130s, BP 110/70. Temp of 102.5F. CXR clear. Normal obstxn series. ED has given him vanc/zosyn. • Differential? • Pathogens? • Tests?

36. Case 4 • 33yoM PMH quadraplegia 2/2 MVA, neurogenic bladder with suprapubic catheter, UTIs, resident of nursing facility, arrives in ED with fever to 101.9F, tachy to 120s, BP is 85/52, RR= 25. He is not vent dependent. • Differential? • Pathogens? • Tests? • Treatments?