Infectious Diseases Potpourri. Disclosures 7/24/2014. No conflict of interest to disclose. Pot-pour-ri \,pō-pu - rē\ noun

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1 Infectious Diseases Potpourri Nick Gilpin, DO Section Head, Infectious Diseases Beaumont Health Systems Grosse Pointe Assistant Clinical Professor, OUWBSOM Assistant Clinical Professor, MSUCOM Presented for the MAOFP Conference August 1-3, 2014 Traverse City, MI Disclosures No conflict of interest to disclose Pot-pour-ri \,pō-pu - rē\ noun : A mixture of dried flower petals, leaves, and spices used to make a room smell pleasant : A miscellaneous collection 1

2 Overview Discuss evaluation and management (including antibiotic selection) for a variety of commonly encountered infectious diseases: Cellulitis; skin and soft tissue infections Pneumonia (community acquired) UTIs Diabetic Foot Infections; osteomyelitis Scenario #1: Cellulitis Case Presentation 44 y/o male with history of pre-diabetes 3 day history of progressive swelling, redness, pain involving his RUE Discovered upon awakening No fevers, chills, other symptoms.. No history of prior cellulitis 2

3 Buzzwords! I got bit by a spider There s this red streaking It s been itching like crazy I had a DVT a while ago My dog bit me Pasteurella multocida A person bit me I was swimming in the ocean S. aureus (MRSA) Eikenella corrodens I was cleaning my fishtank I got this infection after a mud run Group A strep (S. pyogenes) Contact dermatitis? Venous insufficiency? Vibrio vulnificus Mycobacterium marinum Fish-Tank granuloma Aeromonas hydrophila An Evidence-Based Approach First, is it NON-PURULENT or PURULENT: Non-purulent? Think Group A Strep Fiery red, well-demarcated Lymphangitis or streaking No obvious portal of entry Purulent? Think S. aureus Redness surrounding some purulent focus Patient may have some historical clue (e.g., fitness club, close contact, etc.) Blood cultures, skin swabs, and biopsies are LOW YIELD! Helpful if an abscess is present May help diagnose infectious mimics (pyoderma) They may be useful in immunocompromised patients, patients with penetrating trauma, or bites IDSA Practice Guidelines for SSTIs. Clinical Infectious Diseases. 2014;

4 An Evidence-Based Approach For non-purulent cellulitis (Group A Strep): Without systemic signs/symptoms (mild) Oral therapy PCN, Dicloxacillin, Cephalosporin, Clindamycin With systemic signs/symptoms (moderate) Consider hospitalization, IV antibiotics PCN, Cefazolin, Clindamycin With severe signs/symptoms (sepsis), trauma, or suspicion of MRSA (severe) Consider imaging, debridement IV antibiotics Vanco PLUS Zosyn (broad spectrum antibiotics) IDSA Practice Guidelines for SSTIs. Clinical Infectious Diseases. 2014; 1-43 An Evidence-Based Approach For purulent cellulitis (Staph aureus, MRSA): Small abscess without systemic illness (mild) I+D only Culture is optional Abscess/cellulitis with systemic illness (moderate) I+D, culture Oral antibiotics: Bactrim or Doxycycline Maybe Clindamycin? With severe signs/symptoms (sepsis), hypotension (severe) I+D, culture IV antibiotics: Vanco, Linezolid, Daptomycin, etc. IDSA Practice Guidelines for SSTIs. Clinical Infectious Diseases. 2014; 1-43 IDSA Practice Guidelines for SSTIs. Clinical Infectious Diseases. 2014;

5 Remember Adjunctive Therapies Elevate the leg to promote gravity drainage of edema Warm compresses to facilitate drainage of purulent abscesses Limit ambulation Corticosteroids may be beneficial in uncomplicated cases, non-diabetics (shortens healing time by ~1 day) Treat underlying conditions like tinea pedis and eczema to prevent recurrences Decolonization with topical chlorhexidine and intranasal mupirocin may be useful in cases of recurrent MRSA abscesses 5 days of intranasal mupirocin twice daily plus daily chlorhexidine washes Clinical Infectious Diseases 2005; 41: IDSA Practice Guidelines for SSTIs. Clinical Infectious Diseases. 2014; 1-43 How long should I treat?? Depends Uncomplicated cellulitis: About 5 days (maybe more) Complicated (hospitalized) cellulitis: 7-14 days May be significantly longer in patients with unusual pathogens like mycobacteria, fungi, Nocardia, etc. How I approach cellulitis: Oral therapy is preferred If hospitalization/parenteral is required, treat until 60-70% improvement in cellulitis, then transition to oral therapy Clinical Infectious Diseases 2005; 41: IDSA Practice Guidelines for SSTIs. Clinical Infectious Diseases. 2014; 1-43 Scenario #2: Pneumonia 5

6 Case Presentation 70 y/o male is brought to the EC Increased cough, chest discomfort, SOB Some sputum production Feels feverish Not so subtle Guidelines for CAP Guidelines for HCAP 6

7 Is it CAP or HCAP? HCAP Antibiotics within the preceding 90 days Hospitalization in the preceding 90 days ECF resident Home infusion therapy or wound care Family member with MDR pathogen Dialysis within past 30 days CAP No healthcare-associated exposure IDSA Guidelines for CAP. Clinical Infectious Diseases 2007; 44:S ATS Guidelines for HCAP. Am J Respir Crit Care Med ; 2005 ; 171 : CAP Pathogens Outpatient Inpatient ICU S. pneumoniae S. pneumoniae S. pneumoniae Mycoplasma pneumoniae Mycoplasma pneumoniae S. Aureus (MRSA?) Haemophilus influenzae Haemophilus influenzae Legionella species Chlamydophila pneumoniae Chlamydophila pneumoniae Gram-negative bacteria Respiratory viruses Legionella species Haemophilus influenzae Aspiration Respiratory viruses Diagnosis of CAP Remember that pneumonia is a CLINICAL diagnosis (cough, fever, sputum production, chest pain) supported by radiographic findings! All patients with suspected pneumonia should have some form of imaging (CXR or CT) Additional testing (e.g., performing cultures) is discretionary Cultures are often falsely negative or do not impact clinical management Blood cultures are only positive 5-14% of the time Sputum cultures are probably not much better A good rule of thumb: Perform a test only when the result will change your management 7

8 Clinical Infectious Diseases 2007; 44:S27 72 Management of CAP To admit or not to admit CURB-65 (score 2 may warrant admission) Confusion Uremia (BUN 20) Respiratory rate 30 Blood pressure (hypotension) Age > 65 ICU admission? Septic shock and/or mechanical ventilation More than 3 criteria for severe pneumonia Clinical Infectious Diseases 2007; 44:S

9 Treatment of CAP Outpatient Inpatient ICU If previously healthy and no abx in prior 3 months: Azithromycin or clarithromycin alone Doxycycline If comorbidities present or recent abx use: A β-lactam plus a macrolide (e.g., cefuroxime plus azithromycin) A respiratory fluoroquinolone (moxifloxacin or levofloxacin) A β-lactam plus a macrolide (e.g., ceftriaxone plus azithromycin) A respiratory fluoroquinolone (moxifloxacin or levofloxacin) A β-lactam plus either a macrolide or respiratory fluoroquinolone (e.g., ceftriaxone plus azithromycin or moxifloxacin/ levofloxacin) If PCN-allergic, consider aztreonam plus a respiratory fluoroquinolone Have a very low threshold for adding MRSA coverage (e.g., vancomycin or linezolid)! IDSA Guidelines for CAP. Clinical Infectious Diseases 2007; 44:S HCAP Pathogens S. aureus (especially MRSA) Pseudomonas E. coli Klebsiella species Other enteric Gram-negatives Acinetobacter and Stenotrophomonas species Legionella species Aspiration pathogens Polymicrobial Viruses, fungal organisms Almost always multi-drug resistant!! Pathogenesis of HCAP Patients are likely to be colonized with MDR organisms Most cases are bacterial, with a small percentage being polymicrobial The source of pathogens includes: The environment (hospital, ECF, etc.) Devices The transfer of microorganisms from healthcare provider to patient Aspiration ATS Guidelines for HCAP. Am J Respir Crit Care Med ; 2005 ; 171 :

10 HCAP Management Algorithm ATS Guidelines for HCAP. Am J Respir Crit Care Med ; 2005 ; 171 : Treatment of HCAP Early ( 5 days) Onset HCAP or Low Risk of MDR Pathogens* Ceftriaxone OR a respiratory fluoroquinolone OR amoxicillin/clavulanate or ampicillin/sulbactam Late Onset or Risk of MDR Pathogens Anti-Pseudomonal penicillin or cephalosporin (cefepime or piperacillin/tazobactam) PLUS a respiratory fluoroquinolone or aminoglycoside PLUS vancomycin or linezolid *includes patients receiving outpatient antibiotics in the past 90 days, but is mostly discretionary ATS Guidelines for HCAP. Am J Respir Crit Care Med ; 2005 ; 171 : How long should I treat?? For CAP, a 5-7 day course of antibiotics is usually enough For HCAP (including VAP), a 7-8 day course is usually enough Research has not found prolonged courses of antibiotics to be beneficial 10

11 Scenario #3: Urinary Tract Infections Case Presentation 33 y/o female presents with 4 day history of burning with urination, fevers, and chills She also notes back pain, worse on the left side She has had UTIs previously, with the last one being about 6 months ago Guidelines for Acute Cystitis And Pyelonephritis Guidelines for Catheter- Associated UTIs Guidelines for Asymptomatic Bacteriuria 11

12 Diagnosis of UTIs History Ask about prior infections, stones, urological procedures, indwelling catheters, etc. Physical Look for CVA or suprapubic tenderness Urinalysis Urine culture (especially if there is suggestion of upper tract involvement) When to evaluate the urinary tract Pyelonephritis with bacteremia not responding to therapy CT scan (abscess?) Nephrolithiasis Ultrasound or CT scan (hydronephrosis?) Neurogenic bladder Bladder/renal ultrasound (post-void residuals?) Men with a urinary tract infection Prostate exam, ultrasound, post-void residuals, etc. Bug Microbiology of UTIs Acute uncomplicated cystitis Acute uncomplicated pyelonephritis Complicated UTI E. coli 79% 89% 32% 24% S. saprophyticus 11% 0% 1% 0% Proteus 2% 4% 4% 6% Klebsiella 3% 4% 5% 8% Enterococcus 2% 0% 22% 7% Pseudomonas 0% 0% 20% 9% Mixed 3% 5% 10% 11% Other* 0% 2% 21% 46% Catheterassociated UTI *includes S. epidermidis, Candida spp., and other Gram-negatives 12

13 Treatment of Acute Uncomplicated Cystitis Macrobid 100 mg bid x 5 days TMP-SMX DS 1 bid x 3-5 days Fosfomycin 3g in a single dose Fluoroquinolones (e.g., ciprofloxacin) should generally be reserved for selected patients where 1 st line therapy is not feasible β-lactams (cephalexin, amox-clav) should also be reserved for selected patients due to increasing failure rates Amoxicillin by itself should NOT be used empirically (too much E. coli resistance) Guidelines for Acute Cystitis/Pyelonephritis. Clinical Infectious Diseases 2011;52(5):e103 e120 Treatment of Acute Pyelonephritis Pyelo = fever, flank pain, pyuria Remember to obtain a urine culture If hospitalization not required: Fluoroquinolone x 7-10 days β-lactams x days TMP-SMX x days If hospitalization required: Ampicillin/gentamicin, fluoroquinolone, or extended spectrum β-lactams should be given intravenously initially You no longer need to keep the patient hospitalized until they are afebrile Guidelines for Acute Cystitis/Pyelonephritis. Clinical Infectious Diseases 2011;52(5):e103 e120 13

14 Treatment of Other Complicated UTIs If a renal/perinephric abscess is present, it should be drained appropriately and cultures Treatment is generally considered for 2-3 weeks based on treatment response Close urology follow-up is necessary Catheter-Associated UTIs The diagnosis is much trickier... Not all pyuria and bacteriuria means infection! Look for true symptoms New onset or worsening of fever, rigors Altered mental status Malaise or lethargy with no other identified cause Flank pain or costovertebral angle tenderness Acute hematuria Pelvic discomfort; In those whose catheters have been removed, dysuria, urgent or frequent urination, or suprapubic pain or tenderness Guidelines for Catheter-Associated UTI. Clinical Infectious Diseases 2010; 50: Treatment of Catheter-Associated UTIs Selection of antibiotics should be based upon cultures (both old and new) Duration of treatment: 7 days of treatment (based on culture results) is recommended for patients with a brisk response to therapy days is recommended for patients with a delayed response to therapy Shorter durations can be considered in some circumstances Guidelines for Catheter-Associated UTI. Clinical Infectious Diseases 2010; 50:

15 What about prophylaxis for patients with indwelling catheters? For prevention of catheter-associated UTIs, there is no documented benefit with: Antibiotics Methenamine Cranberry products Routine catheter changing Enhanced meatal care Antimicrobials in the drainage bag Catheter irrigation Antimicrobial-coated catheters The best practice: use the catheter for the shortest duration feasible For men, consider condom catheters if appropriate Intermittent catheterization appears to be somewhat better than indwelling catheter use Suprapubic catheters should be considered an alternative to long-term indwelling catheters Guidelines for Catheter-Associated UTI. Clinical Infectious Diseases 2010; 50: What about asymptomatic bacteriuria? What is it? For asymptomatic women, bacteriuria is defined as 2 consecutive voided urine specimens with isolation of the same bacterial strain in quantitative counts >100,000 cfu/ml For asymptomatic men, a single, clean-catch voided urine specimen with 1 bacterial species isolated in a quantitative count >100,000 cfu/ml identifies bacteriuria A single catheterized urine specimen with 1 bacterial species isolated in a quantitative count >1000 cfu/ml identifies bacteriuria in women or men When is asymptomatic bacteriuria treated? Pregnancy Persons with structural/neurological abnormalities of the urinary tract Persons undergoing urologic surgery If you re treating asymptomatic bacteriuria, duration should be 3-7 days (same as for cystitis, based on culture results) Guidelines for Asymptomatic Bacteriuria. Clinical Infectious Diseases 2005; 40: Dilemma #4: Diabetic Foot Infections 15

16 Case Presentation 60 y/o diabetic female Cut my foot on something a while ago Progressively worsening ulceration with drainage No fevers, chills No other complaints How do I know if it s infected? How can I tell if it s a bone infection? Look for classic signs of infection (local inflammation, purulence, and systemic signs/symptoms) Beware of not-so-classic signs Consider using a validated scoring system to aid in diagnosis Example: International Working Group on the Diabetic Foot has a scoring criteria to assist in diagnosis of osteomyelitis (versus a skin/soft tissue infection) 16

17 Diabetic Foot Infections: Presentation MILD MODERATE SEVERE More than 2 of: Any of the following: Patient is systemically toxic or unstable Purulence, erythema, pain, tenderness, warmth, induration Cellulitis >2 cm around ulcer Any cellulitis extending <2 cm around ulcer Infection is limited to skin/superficial tissue No systemic illness Lymphangitis Deep tissue abscess Gangrene Muscle, tendon, joint, or bone involvement Guidelines for Diabetic Foot Infection. Clinical Infectious Diseases. 2004; 39: Diabetic Foot Infections: International Working Group on the Diabetic Foot (IWGDF) has attempted to formulate a criteria-based approach to diagnosis Similar to other diagnostically challenging conditions (e.g., infective endocarditis) Not validated in practice, but appears promising, particularly for osteomyelitis Definite Positive bone culture Pus in bone Atraumatically detached bone fragment removed from ulcer Intraosseous abscess on MRI Probable Visible bone in ulcer MRI showing bone edema with other signs of osteomyelitis Bone sample with positive culture but negative histology Bone sample with positive histology but negative culture Possible Plain X-rays show cortical destruction MRI shows bone edema Probe to bone positive Bone visible ESR > 70 without a reasonable explanation Non-healing ulcer present for >2 weeks 17

18 SCORE PROBABILITY OSTEOMYELITIS IS PRESENT MANAGEMENT 1 definite >90% Treat 2 probable 1 probable + 2 possible 4 possible 50-90% Consider treating, but may require further investigation 2 possible 10-50% Further investigation advised before treatment Berendt et al. Diabetes Metab Res Rev Who should be hospitalized? Patients with a severe infection Selected patients with a moderate infection and significant comorbidities Any patient who is unable to comply with a prescribed regimen Patients who fail an outpatient regimen (maybe ) How should cultures be obtained? If it s not infected, DON T CULTURE IT! For infected wounds, get the deepest and best sample possible Debrided tissue or bone is best Preferable to get cultures OFF antibiotics Guidelines for Diabetic Foot Infection. Clinical Infectious Diseases. 2004; 39:

19 To swab or not to swab Generally deep cultures and/or aspirates are preferred over superficial swabs Two main reasons a swab may be helpful: Identification of resistant pathogens (MRSA, VRE) indicates need for special contact precautions Isolation of MRSA often correlates with deep cultures (other junk not so much) What other diagnostic studies may be helpful? Adjunctive labs and imaging are helpful in the following situations: Patient is not responding appropriately to correct therapy Suspicion exists for a deeper infection All patients with a new diabetic foot infection should have a plain radiograph Guidelines for Diabetic Foot Infection. Clinical Infectious Diseases. 2004; 39: Pitfalls of Osteomyelitis Osteomyelitis can be a significant diagnostic challenge Patients at greatest risk are typically immunocompromised Less likely to have febrile/inflammatory response High risk diabetic patients will frequently have absent sensation in affected areas (e.g., the diabetic foot) The labs may not support your diagnosis 19

20 Labs which may aid in the diagnosis of osteomyelitis WBC (elevated?) Beware: this may be helpful in an acute process, but is rarely helpful in a chronic process ESR/CRP (elevated?) USUALLY elevated, but how much is enough Best utility may be to trend these data over time to monitor clinical response Blood cultures Highest yield in settings of acute hematogenous osteomyelitis or vertebral osteomyelitis Yield is still much less than 50% Imaging which may aid in the diagnosis of osteomyelitis Plain X-ray: Low sensitivity (~15-40%); moderate specificity (~70%) Abnormalities are usually seen days after onset of infection Periosteal Reaction Imaging which may aid in the diagnosis of osteomyelitis MRI: Very sensitive (~85%), somewhat less specific High negative predictive value in appropriate clinical setting Typically regarded as the imaging modality of choice 20

21 Imaging which may aid in the diagnosis of osteomyelitis CT scan: Next best modality when MRI cannot be used Beware metallic artifact in setting of hardware Nuclear modalities: High sensitivity, generally poor specificity Three phase bone scan is reasonable in the appropriate clinical setting Consider nuclear modalities in patients where MRI or CT cannot be reasonably performed Three Phase Bone Scan Uses a radionuclide tracer that accumulates in areas of bone turnover Scans are performed at three points following tracer: immediately after injection (blood flow phase) 15 minutes after injection (blood pool tissue phase) 4 hours after injection ( osseous phase) In osteomyelitis, expect high uptake in all three phases Contrast with cellulitis: NO activity in the osseous phase NOT the same thing as a Triple Tracer Bone Scan (bone marrow scan, bone scan, WBC scan) EARLY Uptake occurs in areas of the L foot in all 3 phases This is consistent with OSTEOMYELITIS 21

22 What treatment? If it s not infected, don t treat (Duh ) Topical antibiotics are probably worthless For infected wounds, consider the severity and degree of infection: Mild-to-moderate infections: target Gram-positive cocci (most common), and think about MRSA Keflex; Cefazolin; Vanco More severe infections: go broad (target Gram-positives AND Gram-negative, and potentially anaerobes) Zosyn; Vanco + Zosyn; Vanco + Cefepime +/- Flagyl Targeting Pseudomonas is probably overrated unless your patient has risk factors or known colonization Once your cultures are back, treat what is growing Guidelines for Diabetic Foot Infection. Clinical Infectious Diseases. 2004; 39: Principle of Antimicrobial Therapy in Osteomyelitis/DFI All antimicrobials should be withheld if possible until percutaneous aspirate or surgical deep cultures have been obtained. ** **Unless patient is sick Microbiology of Osteomyelitis/DFI COMMON (>50%) OCCASIONAL (>25%) S. aureus Strep MTB RARE (<5%) CoNS Enterococcus Dimorphic fungi Pseudomonas Candida E. coli Aspergillus Other Enterobacteriaciae Anaerobes Brucella Salmonella 22

23 Targeted Antimicrobial Therapy in Osteomyelitis/DFI Bug Preferred Alternative MSSA MRSA Strep Enterococcus Nafcillin Cefazolin Vanco Dapto PCN Ceftriaxone Cefazolin PCN or Amp (+/- Gent) Vanco (+/- Rifampin) Linezolid (+/- Rifampin) Vanco Vanco Enterobacteriaceae Ceftriaxone Cipro Pseudomonas Cefepime, Pip-Tazo Cipro Osteomyelitis Buzzwords Post-surgical osteo? Osteo in a sickler? Salmonella Man in a tennis shoe steps on a nail? Spinal osteo in a person from India? Sacroiliac joint osteo? S. aureus Osteo in a dialysis patient? Osteo in IV drug users? S. aureus or CoNS S. aureus, MRSA Pseudomonas MTB S. aureus, Pseudomonas, Candida How long should I treat a diabetic foot infection? Continue antibiotics until the infection is resolved You don t need to treat until the wound is healed!! General rule: 1-2 weeks for mild infections, 2-3 weeks for moderate-to-severe infections Guidelines for Diabetic Foot Infection. Clinical Infectious Diseases. 2004; 39:

24 How long should I treat osteomyelitis? Optimal duration is not well established Lack of prospective trials What do we know? 4 weeks is better than 2 weeks 6 weeks is about how long it takes for debrided bone to be covered by vascularized soft tissue A shorter duration may be reasonable when extensive debridement/amputation is performed Treatment should be given parenterally (if feasible) General Principles of Osteomyelitis Treatment Goal: eradicate infection, restore function Understand that you are potentially fighting a losing battle Antimicrobial therapy alone is not curative in most cases of osteomyelitis Surgical debridement will increase your chances of cure Chronic osteomyelitis (devitalized bone) is virtually incurable with antibiotics alone Consider surgery/amputation Thank you! Infectious Diseases Potpourri Nick Gilpin, DO Infectious Disease Beaumont Health Systems Grosse Pointe 24