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Disclosures
 I have no disclosures.
Top ID Curbside Consult Questions
38th Annual Advances in Infectious Diseases
March 2017
Jennifer Babik, MD, PhD
Assistant Clinical Professor
Division of Infectious Diseases, UCSF
Learning Objectives
Roadmap
 To know the situations in which formal in‐person consultation is preferred over curbside consultation
 A Brief Word on Curbsides vs. Formal Consults
 To develop an approach to common ID questions that arise in the inpatient and outpatient setting.
 Case‐Based Approach to the Top Curbside Consult Questions in ID
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Curbsides vs Formal Consults
Are Curbsides Okay?
 Recent study of 47 curbsides vs. formal consults
 Need to balance patient safety, provider workload, education  Medicine consult  Curbside followed by a formal consult by a colleague
 Curbsided providers were not allowed to look in the chart
 Results:
 Information in curbside was inaccurate/incomplete in 51%
 Formal consult changed Rx in 60% (36% “major changes”)
 If information was inaccurate/incomplete then a formal consult changed Rx in 92% (45% “major changes”)
 Curbside volume in ID  In the literature: 20‐120 curbsides/month  At UCSF Medical Center: 60 curbsides/mo (15 hours/mo)
 Impossible in most practices to convert all curbsides into formal consults
Burden et al, J Hosp Med 2013, 8:31.
Grace et al, Clin Infect Dis 2010, 51:651. Wachter, B. "The Dangers of Curbside Consults... and Why We Need Them."Wachter's World. 29 Apr. 2013. Is This An Appropriate Curbside?
Is This An Appropriate Curbside?
What is the dose of ertapenem when the CrCl is <30?
1. Yes
2. No
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Is This An Appropriate Curbside?
Is This An Appropriate Curbside?
1. Yes
2. No
Is This An Appropriate Curbside?
Is This An Appropriate Curbside?
Theoretically, if a patient has mild cystitis due to VRE that is sensitive to doxycycline, can I use that drug to treat a UTI?
1. Yes
2. No
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What is an Appropriate Curbside?
The Special Case of S. aureus Bacteremia
 The Goldilocks of Curbside Consultation
 Benefit of ID consultation versus no consultation
 Not too simple: the answer can be easily looked up
 Not too complicated: the answer requires nuanced clinical judgment or interpretation of a lot of data
 Just right: Hypothetical, factual question
  adherence to quality indicators for SAB:
 More likely to get echo and repeat blood cultures
 Improved antibiotic choice and duration
  removal of prosthetic devices/source control
  detection of metastatic foci of infection  We also tell our ID Fellows that it should probably be a consult if:
 You need to look up the answer
 It’s early in the year
  risk of relapse   mortality (by 20‐50%)
Saunderson et al, Clin Micro Infect 2015, 21:779. Forsblom et al, Clin Infect Dis 2013, 56:527. Bai et al, Clin
Infect Dis 2015; 60:1451. Paulsen et al, OFID 2016. Vogel et al, J Infection 2016; 72:19.
Curbsides for S. aureus Bacteremia?
Curbside #1
 Curbside consult is associated with:
A 75 y/o man with neurogenic bladder and h/o UTIs presents to clinic with a 2 day history of suprapubic
pain and dysuria. Urine dipstick is positive for leukocyte esterase and nitrite and he is sent out with a prescription for cipro. Urine culture comes back 2 days later with E. coli that is an ESBL producer, resistant to cipro. I called him at home and he is still symptomatic.
 Less identification of deep infectious foci
 Less likely to receive the proper duration of therapy
  90d mortality by > 2‐fold compared to formal consult
 UCSF: automatic formal consult policy at all 3 hospitals for patients with SAB
 Formal consult for SAB is preferred if available
Do I need to admit him to the hospital for ertapenem or are there any oral options?
Forsblom et al, Clin Infect Dis 2013, 56:527. 4
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Which Oral ABx Has the Best Efficacy in ESBL UTI?
1. Fosfomycin
2. Nitrofurantoin
3. Minocycline
4. Cephalexin
Oral Options for ESBL E. coli in the Urine Antibiotic
% Sensitive in vitro
Ciprofloxacin
4‐36
TMP‐SMX
22‐43
Amoxicillin/Clavulanate
11‐70
Nitrofurantoin
58‐94
Fosfomycin
91‐100
Caveat: susceptibilities for ESBL Klebsiella are lower for both fosfomycin (~54‐80%) and nitrofurantoin (14%) Prakash et al, AAC 2009, 53:1278. Liu et al, J Micro Immunol Infect 2011, 44:364. Kumar et al, Infect Dis Res Treat 2014, 7:1. Meier et al, Infect 2011, 39:333. Kresken et al, IJAA 2014, 44:295. Fournier et al, Med Mal Infect 2013, 43:62. Rodriguez‐Bano, Arch Intern Med 2008, 168:1897. Linsenmeyer, AAC 2016, 60:1134.
Clinical Data for Oral ABx in E.coli ESBL Cystitis
What if the Patient has Pyelonephritis?
 Fosfomycin
 Small study in community‐acquired pyelonephritis showing non‐carbapenem = carbapenem
 Several studies in outpatient cystitis as 1 dose or 3 doses qod  94% clinical cure
 Cannot use for pyelo/bacteremia
 MIC not routinely done in most micro labs
 Recommend dosing at 3gm PO qod x 3 doses (or until improvement)
 Nitrofurantoin
 1 study in outpatient cystitis as 14 day course  69% clinical cure
 Cannot use for pyelo/bacteremia
 Avoid if CrCl<60 due to inadequate urine levels, potential for toxicity
 Amoxicillin‐clavulanate
 But, non‐carbapenem group:
 Mostly aminoglycoside or pip/tazo
 Had much lower rates of bacteremia  Bottom line: could consider orals in very select circumstances without bacteremia, but no data
 1 study in outpatient cystitis given as 5‐7d course  93% clinical cure
Falagas et al, Lancet ID 2010, 10:43. Rodriguez‐Bano, Arch Intern Med 2008, 168:1897. Pullukcu et al, Int J Antimicrob Agents 2007, 29:62. Reffert and Smith, Pharmacotherapy 2014, 34:845. Park et al, J Antimicrob Chemother 2014, 69:2848.
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Oral Options for ESBL UTI: Take‐Home points
Curbside #2
 Most data is for E. coli ESBL (limited data for Klebsiella)
A 65 y/o man with ESRD on HD through a tunneled right IJ line is admitted with fever and found to be bacteremic on both line and peripheral cultures with Klebsiella pneumoniae. Line culture turned positive 4
hours before the peripheral culture, indicating the line as the source. He has very poor access options. Do we have to take out the line?
 For mild‐moderate cystitis:
 Oral ABx choice dictated by susceptibilities
 Consider susceptibility testing for fosfomycin if possible  Caution with nitrofurantoin given poor clinical cure rates  Would not use orals if the patient is clinically ill, has bacteremia, or cannot be followed closely
 In very select cases of mild pyelonephritis without bacteremia, could consider orals, but there is no data (and can’t use fosfomycin or nitrofurantoin)
Do You Have to Change the Line?
CLABSI: Diagnosis
1. Yes, it’s a GNR
 Clinical findings at exit site in <3% 2. No, you can consider line salvage
 Catheter tip culture:
 (+) peripheral bcx and > 15 cfu/plate from catheter tip
 80% sensitive, 90% specific
 But >80% of catheters removed unnecessarily
Mermel et al, Clin Infect Dis 2009, 49:1. Safdar and Maki, Crit Care Med 2002, 30:2632.
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CLABSI: Differential Time to Positivity
When to Remove the Line
 Allows for diagnosis without removing the line
 Culture from line + peripheral blood at the same time
 CLABSI = blood culture drawn from central line turns positive at least 2 hrs before the peripheral culture  Test characteristics
Complicated Infections
1. Severe sepsis
2. Persistent bacteremia (>72h of appropriate ABx)
3. Septic thrombophlebitis
4. Exit site or tunnel infection
5. Metastatic infection: endocarditis, osteomyelitis
Virulent Organisms
1. Staphylococcus aureus
2. Pseudomonas
3. Candida
 85‐95% sensitive
 85‐90% specific
 Not as good for Candida (b/c slow‐growing)
Liñares, Clin Infect Dis 2007, 44:827. Bouza et al, Clin Infect Dis 2007, 44:820. Bouza et al, Clin Microbiol Infect 2013, 19: E129. Safdar et al, Ann Intern Med 2005, 142:251.
Line Management for Other Organisms How to Retain an Infected Line (Line Salvage)
 Which patients?
Less aggressive with line removal
Organism
PICC/Short‐term CVC Tunneled Cath/Port HD Catheter
Coag‐negative
staphylococci
Remove or retain
Remove or retain
Remove, retain, or guidewire exchange Enterococcus
Remove
Remove or retain
Remove, retain or guidewire exchange
Other GNRs (not Remove
Pseudomonas)
Remove or retain
Remove, retain or guidewire exchange
Mermel et al, Clin Infect Dis 2009, 49:1
Mermel et al, Clin Infect Dis 2009, 49:1
Use clinical judgment based on:
• Severity of infection
• Access options (talk to renal!)
• Risk of line removal/replacement
 Uncomplicated infections  Not for exit site infections or virulent organisms  Only studied in long‐term catheters  How to treat?
 Give systemic ABx + antibiotic lock therapy for 7‐14 d
 Get surveillance blood cultures (1 wk after Abx stop)
Mermel et al, Clin Infect Dis 2009, 49:1
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What is Antibiotic Lock Therapy?
 Goal is to get supra‐therapeutic ABx
concentrations to penetrate biofilms
 Logistics
 Work with pharmacy and nursing  Mix with heparin, dwell times are variable but usually <48h  Common Abx:
 Gram positives: linezolid, vancomycin, cefazolin
 Gram negatives: ceftazidime, ciprofloxacin, gentamicin
Line Salvage with Antibiotic Lock Therapy
Overall Success Rate (%)
100
100
90
90
80
>90%
70
60‐75%
50
60
90%
80%
50
40
40
30‐45%
20
40‐55%
30
20
10
0
80
70
60
30
Abx Lock Efficacy by Organism (%)
10
Systemic Systemic Line Abx
Abx + Lock removal
0
CoNS
GNRs S.aureus
Mermel et al, CID 2009, 49:1 Aslam et al. JASN 2014;25:2927. Fernandez‐Hidalgo and Almirante, Expert Rev Anti‐Infect Ther 2014, 12:117. Ashby et al, Clin J Am Soc Nephrol 2009, 4:1601. Beathard, JASN 1999, 10:1045. What About Guidewire Exchange? Line Management: Take‐Home Points
 Goal is to eliminate biofilm
 Differential time to positivity (line positive ≥ 2 hours before peripheral) allows for diagnosis of CLABSI without line removal
 How good is it?  Limited data, mostly HD catheters
 Seems at least equal to ABx lock (~70% cure), maybe better
 Likely better than ABx lock for S. aureus
 When to consider using?
 If HD catheter removal is clearly indicated but not feasible (especially for S. aureus)  If you want to salvage an HD line but can’t use lock therapy
 All lines should be removed for:
 Any complicated infection
 S. aureus, Pseudomonas, or Candida
 Line management for other organisms depends on line type (lower barrier to remove line for short term catheter > long‐term catheter > HD catheter)
 Use antibiotic lock when possible for line salvage
Robinson et al, Kidney Int 1998, 53:1792. Shaffer, Am J Kid Dis 1995, 25:593. Mokrzycki et al, Dial Transpl 2006, 21:1024. Aslam et al. JASN 2014;25:2927
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Curbside #3 Do You Need to Treat the VRE?
55 y/o woman in the ICU after a complicated spinal surgery. She remains intubated, spikes a fever on POD#3 and is pan‐cultured.  She has thick secretions and a new CXR infiltrate.  mBAL is growing MRSA.
 UA (catheter): 25‐50 WBC, Ucx
positive for VRE.
Asymptomatic Bacteriuria
ASB = (+) urine culture AND no signs/symptoms of UTI
1. Yes
2. No
3. Not sure
Asymptomatic Bacteriuria is COMMON!
 Seen in up to:  25% of elderly, diabetic, or HD patients  50% of patients in long term care facilities
 25% of patients with short‐term catheters, ~100% with long‐term catheters  Of positive urine cultures obtained on the wards after hospital admission  ~90% are ASB
Nicolle et al, Clin Infect Dis 2005, 40:643. Leis et al, Clin Infect Dis 2014, 58:980
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Hazards of ASB Treatment
 Side effects of antibiotics
  risk of Cdiff
  risk of resistance Exceptions: Who With ASB Should Be Treated?
 Pregnant women
  risk pyelo, premature delivery
 GU procedures w/mucosal bleeding
  post‐procedure bacteremia/sepsis  Immunosuppressed patients?
 May increase risk of recurrent UTI by getting rid of “good” interfering bacteria Cai et al, Clin Infect Dis 2012;55(6):771. Cai et al, Clin Infect Dis 2015;61(11):1655..
 Renal transplant in the first 3 months?
 Neutropenia?
Nicolle et al, Clin Infect Dis 2005, 40:643.
What About Patients Undergoing Arthroplasty?
The Heart of the Problem
 ASB is associated with  risk of PJI, but:
 It’s Hard to Ignore a Positive Culture
 Treatment for ASB does not  risk of joint infection
 Bacteria isolated in urine ≠ bacteria isolated in joint
 No  risk of post‐operative UTI
 ASB is likely a surrogate marker of infection risk  Pre‐op screening, treatment of ASB not recommended
Sousa et al, Clin Infect Dis 2014;59:41. Duncan, Clin Infect Dis 2014;59:48.
 Proof of concept study:
 At Mount Sinai, 90% of their inpatient urine cultures were ASB, and 50% were treated with ABx
 They stopped reporting these (+) urine cultures in the EMR
 Results:
 The % of ASB that was treated dropped by 80%
 No untreated UTIs and no sepsis Leis et al, Clin Infect Dis 2014, 58:980.
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What if I Can’t Assess Symptoms?
How To Distinguish ASB vs. UTI?
 Does the UA help?  Yes, but only if negative
How to define UTI in patients with a catheter or AMS?
 Pyuria is very common in ASB, e.g. >50% of catheterized patients with ASB
 But the absence of pyuria suggests an alternative dx
 Always order a UA when ordering a urine culture
Signs/symptoms consistent w/ UTI  Does the organism help?  NO
• Fever, rigors, AMS, malaise  The same organisms cause ASB and UTI (even Pseudomonas and ESBL)
AND
No other source of infection (i.e., diagnosis of exclusion)
• Flank pain, CVAT, pelvic pain
• Acute hematuria
• Spinal cord injury: spasticity,  Use clinical context – does the patient have signs/symptoms of UTI?
autonomic dysreflexia, unease
Nicolle et al, Clin Infect Dis 2005, 40:643. Tambyah et al, Arch Intern Med 2000, 160:678. Lin et al, Arch Int
Med 2012, 172:33.
How to Interpret Urine Studies in a Patient With a Foley or AMS
U/A, urine cx (‐)
Do not treat for UTI
 Pyuria ≠ UTI, but its absence points to a different source
No
Yes
Send U/A, urine cx
U/A (‐), urine cx (+)
Asymptomatic bacteriuria
ASB vs. UTI: Take‐Home Points
 ASB is common, especially in catheterized patients
Alternate Diagnosis Likely?
(Signs/ sx of other illness present)
Do not order U/A, urine cx
Nicolle et al, Clin Infect Dis 2005, 40:643.
 ASB does not require therapy except for:
U/A (+), urine cx (+)
U/A (+), urine cx (‐)
Treat for UTI
(If no alternate dx identified)
Do not treat
 Pregnancy
 Urologic procedures
 Neutropenia, renal transplant <3 mo?
 To diagnose a UTI in a patient with a catheter or who cannot report symptoms, the patient must have:
 Signs and symptoms compatible with UTI  No other source for infection (i.e., diagnosis of exclusion)
Slide courtesy of Catherine Liu. 11
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Curbside #4 What Would You Send Him Out On?
75 y/o M with multiple comorbidities admitted with pneumonia. He is started on ceftriaxone/doxycycine. Sputum culture and blood cultures grow Streptococcus pneumoniae (pan‐susceptible). He improves rapidly and by hospital day 3 he is afebrile, WBC has normalized, and he is ambulating without oxygen.
1. Ceftriaxone 1gm IV daily x 14 days
Should He Be Observed in the Hospital on PO Abx?
Bacteremic Pneumococcal Pneumonia
1. Yes
 When ok to switch to oral therapy?
2. No
2. Levofloxacin 750mg PO daily x 14 days
1. Amoxicillin 1gm PO tid x 7 days
 When clinically stable (symptoms improving, WBC decreasing, afebrile, able to take PO ‐ most by day 4)  No endocarditis or meningitis
 No need to observe in the hospital after IV  PO switch (no difference in 14d readmission rate or 30d mortality)
 Which Abx? (I choose based on disease severity)
 High dose amoxicillin (1gm PO tid)
 Levofloxacin 750mg PO daily
 How long?
 7‐10 days Ramirez and Bordon, Archives 2001, 161:848. Nathan et al, Am J Med 2006, 119:512. Dunbar, Clin Infect Dis 2003, 37:752. Siquier et al, JAC 2006, 57:536.
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Curbside #5
An Indeterminate QFT Means:
1. Intermediate probability of LTBI
2. Borderline/equivocal result 23 y/o woman with Takayasu arteritis on prednisone who needs escalation of immunosuppression to infliximab. She has had an indeterminate QuantiFERON (QFT) x 2, negative PPD, and no lung pathology on chest CT. She is US‐born and has no known TB exposures or other risk factors. Should she be treated for latent TB infection (LTBI)?
QuantiFERON Interferon Gamma Release Assay (IGRA) 3. Low level positive result
4. The test didn’t work
Definition of an Indeterminate Assay
Indeterminate = TEST FAILURE
Incubate
1) Nil tube: Negative control
2) TB antigen tube: • ESAT‐6 + CEP‐10
• Not in BCG or most NTM
3) Mitogen tube: Positive control
Measure IFN‐γ
by ELISA
Positive control (mitogen) didn’t work Negative control (nil) had too much background IFN‐γ
>85% of indeterminate results
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How Common is an Indeterminate QFT?
Reasons for an Indeterminate QFT
 HCWs and TB Screening Programs: 1%
Test Factors
Patient Factors
 Volume of blood drawn
 Suboptimal handling
 Delays from blood draw to incubation step  Immunocompromise
impairs ability of T cells to produce IFN‐γ in response to mitogen
 Tertiary care inpatient setting: 20%
 UCSF Medical Center inpatient results (2016)
 Negative: 60‐70%
 Positive: 8‐12%
 Indeterminate: 18‐24%
Fabre, Open Forum Infect Dis 2014. Lucet al al, Infect Contrl Hosp Epi 2015, 36:569. Simpson et al, J Immigrant Minorty Health 2013, 15:686.
Pai et al, Clin Micro Rev 2014, 27:3.
Indeterminate QFT and Immunocompromise
How to Manage Indeterminate QFT?
% indeterminate results
70
60
60
 If high risk patient  repeat and/or perform a PPD
 Repeat QFT 50
 May eliminate possibility of lab‐related factors
 Many will still be indeterminate (40‐70%)
 Consider waiting until CD4 is higher or immunosuppression is decreased
40
30
20
20
10
1
15
15
HIV
(CD4<100)
SLE
5
0
HCWs
HIV
SOT/HSCT
Critical
illness
 In a high risk patient, use epidemiologic risk factors, clinical history, chest imaging
Cho et al, Lupus 2016; 0:1. Huang et al, Sci Rep 2016; 6:19972. Sester et al, Am J Respir Crit Care Med 2014, 190:1168. Leutkemeyer et al, Am J Respir Crit Care Med 2007, 175:737. 14
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Indeterminate QFT: Take‐Home Point
Curbside #6
 Indeterminate QFT = test failure due to failure of either the positive (most likely) or negative control
A 45 y/o woman with diabetes is admitted with pyelonephritis. Her urine and 2 blood cultures are positive for pan‐sensitive Klebsiella pneumoniae. She was treated empirically with ceftriaxone and has improved (defervesced, normalized her WBC count, resolution of symptoms). When can she change to PO therapy and how long do we need to treat for? I want to use cephalexin because this is the most narrow antibiotic – is this okay?
She Should Finish a Treatment Course With:
When is it Ok to Change to PO Therapy?
1. Ceftriaxone IV x 14 days
 Meta‐analysis of early‐switch (days 1‐4) vs late switch (days 7‐10) to PO therapy showed no difference in clinical outcome
2. Ciprofloxacin IV x 7 days
3. Ciprofloxacin PO x 7 days
 Studies included beta‐lactams, TMP‐SMX, cipro
 Caveat: 6 of the 8 studies were in children
 Bottom line: when is it ok to change to PO?
4. Cephalexin PO x 7 days
 When susceptibilities are known
 When patient has defervesced and clinically improved
Vouloumanou et al, Curr Med Res Opin 2008, 24:3423.
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RCTs on Short Course Therapy for Pyelonephritis
Short Course Therapy for Pyelonephritis
Study
ABx Results
Patients
Bacteremia
Talan et al 2000
Cipro 500mg PO bid x 7d superior to TMP‐SMX 1 DS PO bid x 14d
Uncomplicated pyelo
5%
 Recent systematic review of short vs long course therapy for pyelonephritis
 Patients
Peterson et al Levo 750mg PO qday x 5d = 2008 cipro 500mg PO bid x 10d Uncomplicated and complicated pyelo
2%
Sandberg et al Cipro 500mg PO bid for 7d = 2012
cipro 500mg PO bid for 14d Uncomplicated pyelo
27%




8 RCTs, 2515 patients
Uncomplicated and complicated pyelo
Most studies compared fluroquinolones
3‐29% of patients bacteremic
 Results
 Short course (≤7d) = long course (>7d)  Exception: Micro cure rates in short course were lower in pts
w/urogenital abnormalities
Talan et al, JAMA 2000, 283:1583. Peterson et al, Urology 2008, 71:17. Sandberg et al, Lancet 2012, 380:48. Eliakim‐Raz et al, J Antimicrob Chemother 2013, 68:2183. Treatment Recommendations for Pyelonephritis
PO Therapy for Pyelonephritis: Take‐Home Points
Uncomplicated Pyelo (IDSA)
Complicated Pyelo
 Fluoroquinolones
 No guidelines exist
 Ok to change to PO therapy once the patient is improving clinically
 Cipro 500mg PO bid x 7 days (A‐I)
 Levo 750mg PO daily x 5 days (B‐II)
 TMP‐SMX  TMP‐SMX 1 DS PO bid x 14 days (A‐I)
 Beta‐lactams
 Oral beta lactam x 10‐14 days (B‐III)
 Lower efficacy than other regimens
 If bacteremia would be wary as serum levels will be lower than can be achieved with FQ or TMP‐SMX
 Most would treat for 7‐14 days as per uncomplicated pyelo
 If urogenital abnormalities, consider treating for 14 days
 First choice oral therapy is a fluoroquinolone
 Duration in most cases can be short (≤7 days) with a fluoroquinolone
 Duration should be longer with TMP‐SMX (14 days) and beta‐lactams (10‐14 days) and the latter should be used with caution in patients with bacteremia
Gupta et al, Clin Infect Dis 2011, 52:e103.. 16
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Curbside #7
Can you ignore Candida in the urine?
I can ignore Candida in the urine, right?
1. Yes, in most cases
1. No, Candida is a frequent cause of UTI
Candiduria: Who Needs Treatment? Candida UTI: Treatment Options
 Candiduria is very common in cathetrized patients
 Fluconazole is the drug of choice
 Candiduria is usually asymptomatic
 Excellent urine levels
 In general, don’t treat! (exceptions: same for ASB)
 Change the foley: can eliminate candiduria in 20‐40%
 Symptomatic candiduria (uncommon)
 Look for same symptoms as bacterial UTI
 Treat if you are convinced
Pappas et al, Clin Infect Dis 2009, 48:503.
 10‐fold higher than in serum
 Can get levels > MIC for fluc‐resistant species like C glabrata
 What about a fluconazole‐resistant organism?
 Try fluconazole and re‐check a urine culture
 Other options: flucytosine, conventional amphotericin
 Other azoles, echinocandins have poor urinary penetration
Fisher et al, Clin Infect Dis 2011, 52:S457.
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Thanks For Your Attention!
 Questions?
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