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4/15/2014
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Difficult ID Decisions in Primary Care Clinic
Sarah Doernberg, MD, MAS
4/23/14
Outline
• Management of urinary tract infections due to extended‐spectrum β‐lactamase producing bacteria
• QTc concerns
• Scabies
• Infection control in the clinic
• Conclusion
Case #1
• 63 y/o F with multiple sclerosis and neurogenic bladder with a history of recurrent UTIs presents to you complaining of 1 day of dysuria and suprapubic tenderness. She denies fevers and appears well. Her vital signs and exam are normal. You order a UA and urine culture and receive the following results:– UA: +LE, +nitrites, 20‐50 WBCs, trace epis– Culture: >100,000 E. coli (R = ceftriaxone, amoxicillin‐clavulanate, TMP/SMX, ciprofloxacin; Sn = ertapenem, gentamicin)
You are concerned that this is an ESBL‐producing organism. What do you do?
1. Admit her to the hospital, place a PICC line, and start IV ertapenem
2. Arrange for IM injections of gentamicin x 7 days
3. Treat with amoxicillin‐clavulanic acid 500 mg/125 mg PO x 5 days
4. Treat with fosfomycin 3 g PO x 1
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What is an ESBL?
• Plasmid‐encoded bacterial enzyme
• PCN, cephalosporin, monobactam resistance
• Usually (50‐70%) resistant to others, too—TMP/SMX, FQs
• Heterogeneous enzymes producing resistance
• Resistance from other mechanisms
– Treatment approach may be similar
Paterson DL. Clin Microbiol Rev 2005; 18: 657‐686.
Risk factors for community ESBLs
• Age
• Male gender
• DM
• Prior hospitalization
• Prior FQ or cephalosporin use
• Prior hospital admission
• K. pneumoniae
Rodriguex‐Bano J and Navarro MD. Clin Microbiol Infect 2008; suppl 1: 104‐110.
Nitrofurantoin
• 40‐50% oral bioavailability
– Low tissue levels but high in the urine
– Do not use in renal failure
• 71% of ESBL E. coli isolates susceptible
• ~70% success rate for ESBL E. coli lower UTIs
Sorlozano Puerto A. Diagn Microbiol Infect Dis 2006; 54: 135‐139.
Clavulanic acid combinations
• Very effective inhibitor of most ESBLs• Compounded w/ amox
– Easily hydrolyzed by ESBLs– High urinary levels help overcome resistance– Dose 500 mg/125 mg PO q8 hours x 5‐7 days
• 31/37 (84%) cure in observational study– 94% (17/18) in those with MIC ≤ 4– 90% (9/10) in those with MIC = 8– 75% (3/4) in those with MIC = 16– 40% (2/5) in those with MIC ≥ 32
Livermore DM, et al. Clin Microbiol Infect 2008; 14 S1: 189‐193; Rodriguez‐Bano J, et al. Arch Intern Med 2008; 168: 1897‐1902
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Other β‐lactams plus clavulanate
• Some centers are using amox‐clavulanate + cefpodoxime or cefixime for lower UTI due to ESBL organisms
– Dosing schedule does not match up fully
Livermore DM, et al. Clin Microbiol Infect 2008; 14 S1: 189‐193
Sensitive (≤1) Resistant (>1)
E. coli Cefpodoxime 0 380
+clavulanate 340 40
Klebsiella Cefpodoxime 3 223
+clavulanate 205 21
Fosfomycin
• Inhibits cell wall synthesis, unique MOA
• 3 g powder mixed with fluid x 1 dose
– QOD x 3 or more for complicated infections
• Resistance < 3% in outpatients with UTI
– E. coli less resistant than Klebsiella spp.
• Susceptibility testing often a send‐out
• 94% clinical cure rate
FalagasME, et al. Lancet ID 2010; 10: 43‐50; Pullucku H, et al. Int J Antimicrob Agents 2007; 29: 62‐65
Which one to choose?
Antibiotic Pros Cons
Nitrofurantoin Well‐toleratedInexpensive
4x/dayNot in renal dzNot for upper tract
Amoxicillin‐clavulanic acid
Well‐studied in UTI Side effectsLess effective
Cefpodoxime+amox‐clavulanicacid
Potential benefit in ascending infections
Dosing schedule does not match upTwo antibiotics
Fosfomycin Easy to takeWell‐tolerated
ExpensiveCaution w/ renal dzSend‐out for susceptibility
Back to our case…
1. Admit her to the hospital, place a PICC line, and start IV ertapenem
2. Arrange for IM injections of gentamicin x 7 days
3. Treat with amoxicillin‐clavulanic acid 500 mg/125 mg PO x 5 days
4. Treat with fosfomycin 3 g PO x 1
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Take‐home
• ESBL‐producing organisms are becoming more common in the community
• Prior antibiotic and healthcare exposure are major RFs
• Oral treatment options include nitrofurantoin, amoxicillin‐clavulanic acid, other clavulanicacid combinations, and fosfomycin
Outline
Management of urinary tract infections due to extended‐spectrum β‐lactamase producing bacteria
• QTc concerns
• Scabies
• Infection control in the clinic
• Conclusion
Case #2: You have a patient with a history of dilated cardiomyopathy who has prostatitis, which you would like to treat with 21 days of antibiotic. Which antibiotic should prompt an EKG before treatment?
1. Cephalexin
2. Amoxicillin/clavulanic acid
3. Ciprofloxacin
4. Doxycyline
QTc concerns
• QT includes depolarization + repolarization– Large variability– Affected by gender, age, autonomic tone, heart rate, drugs, electrolytes, ischemia
• Torsades de pointes is polymorphic VT associated with ↑QT interval
• Certain medications can prolong QTc• Difficult to study
– No standardized preclinical model– Trials not usually powered to detect changes– Often identified in post‐marketing studies and reports– Mandated risk assessment started in 2005
Goldstein EJC, et al. Clin Infect Dis 2006; 43: 1603‐1611.
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Multiple “hits” predispose to Tdp
Goldstein EJC, et al. Clin Infect Dis 2006; 43: 1603‐1611.
Underlying cardiac dz
Electrolyte abnl
Lack of dose adjustment in renal/hepatic impairment
Concurrent CYP inhibitors
Slow genetic metabolism
Other QTcliable drugs
TdP
QTc liable drug
Main antibiotics of concern
• Macrolides
• Quinolones
• TMP/SMX
• Triazoles
• Certain HIV medications
– Atazanavir, ritonavir, saquinavir, rilpiverine
• Others
http://crediblemeds.org/everyone/composite‐list‐all‐qtdrugs/?rf=US
Azithromycin and cardiac death
Ray WA et al., N Engl J Med 2012; 366: 1881‐90
The story is not so straightforward…
Svanstrom H et al., N Engl J Med 2013; 368: 1704‐12
Antibiotic use Azithro vs. No abx Azithro vs. PCN
Current 2.9 (1.1‐7.2) 0.9 (0.6‐1.6)
Recent 1.4 (0.5‐1.5) 0.8 (0.3‐1.6)
Past 0.7 (0.4‐1.2) 0.9 (0.6‐1.4)
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Death by cardiovascular risk
Ray WA et al., N Engl J Med 2012; 366: 1881‐90
Risk varies by macrolide
• Telithromycin
• Clarithromycin
• Erythromycin
• Azithromycin
Fluoroquinolones
• Interfere with the potassium channel responsible for cardiac repolarization
• Many reports of TdP for all FQs
• Multifactorial
– 24% with additional QTc prolonging drugs
– 62% with cardiac disease
– 17% electrolyte abnormalities
• Ciprofloxacin appears safest
Goldstein EJC, et al. Clin Infect Dis 2006; 43: 1603‐1611.
Recommendations
• Avoid QT‐prolonging drugs in anyone with a QT>440ms (female) or 420ms (male)
• Do not allow the QT to exceed 500ms
• Adjust dose for organ dysfunction
• Be aware of drug interactions
– CYP interactions
– Concurrent QTc liable drugs
http://crediblemeds.org/healthcare‐providers/professionalfaq/
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What to do if you suspect a serious adverse drug reaction?
• Stop the medication and find an alternative
• Treat the reaction
• Report to FDA MedWatch: https://www.accessdata.fda.gov/scripts/medwatch/
Take‐home
• Several antibiotics have been associated with prolonged QTc and sudden death
• Small increased risk
• Risk is likely associated with underlying cardiovascular comorbidities and other liabilities
• Screening EKG reasonable for those at high risk
Outline
Management of urinary tract infections due to extended‐spectrum β‐lactamase producing bacteria
QTc concerns
• Scabies
• Infection control in the clinic
• Conclusion
Case
• A 30 y/o M presents to your office with intense, diffuse pruritis. His girlfriend is asymptomatic. They deny any new detergents, soaps, or medications. Exam reveals:
www.uptodate.com; Chosidow O. NEJM 2006; 354: 1718‐27
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How do you treat this patient?
1. Lindane 1% lotion, wiped off after 8 hours to the patient alone
2. Lindane 1% lotion, wiped off after 8 hours to the patient and his girlfriend
3. Permethrin 5% cream, wiped off after 8‐14 hours to the patient alone
4. Permethrin 5% cream, wiped off after 8‐14 hours to the patient and his girlfriend
5. No treatment needed
Sarcoptes scabiei
• Obligate human parasite
• Female mites
– 5‐15 in classic scabies
– Hundreds‐millions in crusted scabies
• Crawl 2.5 cm/min
• Live 24‐36 h off humans
• Spread via contact
• Incubation 2‐6 weeks
– Shorter if prior ifxnChosidow O. NEJM 2006; 354: 1718‐27
Crusted scabies
• AKA “Norweigan scabies”• Same organism, different host• More infectious• Superinfections more common
www.webmd.com; www.aad.org
Diagnosis
• Clinical picture
• Distribution of rash
• Burrows and nodules– Specific but not sensitive
• Pruritis worse at night
• Skin scrapings
• Occasionally, biopsy for atypical cases
http://www.cdc.gov/dpdx/scabies/index.html
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How to do a skin scraping
• Mineral oil to skin– No excoriations– No inflammation
• Scrape with scalpel or slide– 90 degrees to skin– No blood
• 6 sites• Tap onto slide• 1‐2 drops mineral oil
Management
• Treat patient and contacts simultaneously
– Even if asymptomatic
• Wash laundry at > 60°C after the first Rx
– Or leave in sealed bag x 72 hours
• Return to work/school the day after treatment
• Isolate pts with crusted scabies
Chosidow O. NEJM 2006; 354: 1718‐27
Treatment optionsName FDA? Route Pregnancy
categoryComments
Permethrin Yes Topical B 1st‐line topical rxMust apply correctly
Lindane Yes Topical C Not for kidsNeurotoxic
Crotamiton Yes Topical C Not effectiveScabies nodules
Ivermectin No Oral C + eczema/open wounds1 dose inf to permethrinin RCT but 2 doses equal
Precipitatedsulfur
No Topical None Limited dataThought safe for kids
Chosidow O. NEJM 2006; 354: 1718‐27
Ongoing pruritis
Chosidow O. NEJM 2006; 354: 1718‐27
Cause Rx
Overtreatment Emollients +/‐ topical steroids
Eczematous scabies Emollients
Contact dermatitis Topical steroids
Failure to treat properly Oral ivermectin
Resistance Use another scabicide
Relapse/reinfection Further scabicideTreat contacts
Delusions of parasitosis Psychiatric referral
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Take‐home
• Scabies generally is a nuisance
• Recognition of crusted scabies is important
• Clinical dx most common, can do scrapings
• Treat contacts
• Treat linens/clothes
• Topical and PO options available
Outline
Management of urinary tract infections due to extended‐spectrum β‐lactamase producing bacteria
QTc concerns
Scabies
• Infection control in the clinic and at home
• Conclusion
Disease transmission in the outpatient setting
Mode of transmission Reported agents
Common source NTM AdenovirusHepatitis B LegionellaBacteria
Airborne MeaslesMTBRubellaVaricella
Person‐to‐person/droplet Adenovirus Other virusesPertussis Scabies/liceFlu
Goodman RA, Solomon SL. JAMA 1991; 265: 2377‐81; Herwaldt LA et al., Infect Control Hosp Epidemiol 1998; 19: 41‐74; Sepkowitz KA. Ann Int Med 1996; 125: 826‐34
Outpatient infection control challenges
• Hard to define exposed population– Open registration areas, waiting rooms, etc.
• Inadequate triage– Registration often by those w/ less medical knowledge
• Clinics not designed for infection control – No negative pressure
– One entrance/exit
– Recirculated air
Herwaldt LA et al., Infect Control Hosp Epidemiol 1998; 19: 41‐74
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Case
• You are reviewing your case panel for the day and see that your third patient, who is new to your practice, has a chief complaint of chronic cough.
What should be done when this patient arrives?
1. He should be checked into the waiting room and called for his appointment as usual
2. He should be screened for TB risk factors and sent to the ED if positive
3. He should be screened for TB risk factors and masked if positive
4. He should be screened for TB risk factors, masked, and placed in an exam room if positive
Triage for TB in the real‐world
• 2/55 (4%) isolated at triage
• 26 (47%) isolated in the ED
• 17/44 (30%) on admission
• 4/44 (8%) after admission
• Median time from registration to isolation = 8 hours
• Reported attack rates 20‐76%
Herwaldt LA et al., Infect Control Hosp Epidemiol 1998; 19: 41‐74; Moran GJ et al., Ann Emerg Med 1995; 26: 283‐289; Sepkowitz KA. Ann Int Med 1996; 125: 826‐34
Herwaldt LA et al., Infect Control Hosp Epidemiol 1998; 19: 41‐74
Persistent cough?
Yes
Contact with someone sick with TB?
+PPD/QFT?
Rx for TB in past?
Birthplace/travel to at‐risk regions?
Nursing home, jail, shelter contact?
Yes
Negative‐pressure room, if available
Door closed
Surgical mask for patient
N95 for provider
No
No
Stop
Proposed triage algorithm for TB
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Case
• Your second patient of the day arrives with her son. They both have had several days of fever and now have developed a rash. The son was not immunized due to parental concerns about vaccines.
What do you need to do now?
1. Send the patient directly to the ED
2. Examine the patient and make a plan for diagnostic testing and treatment
3. Paper mask for the patient and her son, N95 mask for you, shut the door
4. Contact your department of public health
5. 1 and 4
6. 2, 3, and 4
Measles exposures in the clinic
• 3‐30% acquired in US via healthcare exposure
– RR with health‐care visits: 2.1‐8.4
• 5‐10% of HCWs non‐immune to measles
• Infectious period:
– 4 days before the rash until 4 days after the rash
Herwaldt LA et al., Infect Control Hosp Epidemiol 1998; 19: 41‐74; Sepkowitz KA. Ann Int Med 1996; 125: 826‐34
Prevention of measles
• Triage of patients with fevers/rash– Schedule at end of the day, separate entrance if avail– Paper mask for patient, N95 for provider– Go directly to exam room– Negative pressure or fans in windows if possible
• Vaccinate HCWs and patients• Report to your health department• Post‐exposure prophylaxis for those at high‐risk• Home quarantine dd 5‐21 for exposed pts and HCWs
Herwaldt LA et al., Infect Control Hosp Epidemiol 1998; 19: 41‐74; http://www.cdph.ca.gov/programs/immunize/Documents/CDPHMeaslesInvestigationQuicksheet.pdf
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Case
• You are scheduled for a discharge follow‐up appointment with a 73 y/o wheelchair‐bound patient with history of CVA, who recently was admitted to the hospital for urosepsis. His hospital course was complicated by C. difficilecolitis, for which he is being treated with a 14‐day course of oral vancomycin. He was discharged 10 days ago.
How do you manage the patient in light of the history of recent C. diff?
1. Cancel his appointment: You don’t want to risk C. diff spreading to yourself or your patients!
2. See him as usual, no need for any change in practice
3. See him at the end of the day, wear gloves, and clean the exam room with bleach after his visit
C. diff spread in the outpatient setting
• Recently discharged outpatients with CDI
• 81% had at least 1 outpatient visit within 12 weeks
• 13/44 (31%) with perirectal colonization
• 14/44 (32%) had skin contamination
• Risk factors for shedding:– Older age
– Receipt of non‐CDI antibiotics
– Incontinence
– Decreased mobility
• 14% of randomly swabbed outpt settings had C. diff
Jury LA et al., PLOS One 2013; 8(7):e70175. doi: 10.1371/journal.pone.0070175. Print 2013.Jury LA et al., PLOS One 2013; 8(7):e70175. doi: 10.1371/journal.pone.0070175. Print 2013.
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Proposed algorithm for outpatients
Jury LA et al., PLOS One 2013; 8(7):e70175. doi: 10.1371/journal.pone.0070175. Print 2013.
Recent CDI
2‐6 weeks prior
On vanc taper No change
Not on vancImmobile or incontinent
≤2 weeks Enhanced precautions
Infxn control for outpatients w/ C. diff
• Dedicated commode at home
• Wash with soap and water
• Clean bathrooms and other high‐touch surfaces with bleach
How do you manage the patient in light of the history of recent C. diff?
1. Cancel his appointment: You don’t want to risk C. diff spreading to yourself or your patients!
2. See him as usual, no need for any change in practice
3. See him at the end of the day, wear gloves, and clean the exam room with bleach after his visit
Take‐home
• Train front‐line staff to triage in order to promptly isolate
– Minimize exposure to other patients
• Use appropriate personal protective equipment
• Protect yourself with immunizations
– Post‐exposure prophylaxis when necessary/available
• Report suspected cases of communicable diseases to the appropriate authorities
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QUESTIONS?