Update on Revised McGeer Criteria, Clostridium difficile Infections (CDI) and UTIs in the Long Term Care Facility

1
Update on Revised McGeer Criteria, Clostridium
difficile Infections (CDI) and UTIs in the Long
Term Care Facility

• Edward C. Oldfield, III, MD
• Virginia Medical Directors Association
• September 29, 2012

2
Ageing Population

• By 2030, 20 of the U.S. population will be over
  65 years old.
• Currently, gt 16,000 nursing homes/LTCFs with 1.5
  million residents in the U.S.

3
Infections in the LTCF

• Infections in LTCFs are more frequent than
  hospital acquired infections about 2.5 million
  each year.
• Infections cause 25-50 of all hospital transfers
  or 250,000 admissions each year.
• 30-50 of all hospital admissions for those over
  65 y.o.
• Over 100,000 deaths in LTCFs each year at a cost
  of 1 billion.

4
Antibiotics and Nursing Homes

• 54 of nursing home patients receive a course of
  antibiotics each year.
• Most common indication is for urinary tract
  infections 36 of all antibiotics.
• 9 of all prescriptions are for asymptomatic
  bacteriuria, which is inappropriate.
• Warren J. J Am Geriatr Soc
  199139963-72.

5
Infection Control in LTCFs

• LTCFs pose multiple challenges to infection
  control
• High prevalence of infections.
• High rates of colonization with antimicrobial
  resistant organisms.
• Frequent and often inappropriate prescribing of
  antimicrobials.
• Moro M. Infect Control Hosp Epidemiol.
  201233978-80.

6
Infection Control in LTCFs

• Frequent transfer of residents from the hospital.
• Growing elderly populations with increasingly
  complex medical problems.
• Scarce resources.
• Absent/poor coordination of clinical and nursing
  care.

7
The Perfect Storm of Antimicrobial Resistance
8
Surveillance in LTCFs

• Surveillance of infections is universally
  recommended as the core of infection control
  efforts.
• Increases awareness of the problem.
• Establishes an infection control presence in
  the facility.
• Identifies critical areas for infection control.
• Determines trends.
• Identifies and prevents outbreaks in a timely
  fashion.

9

• Mc Geer Criteria. Definitions of Infections in
  Long Term Care Facilities. Am J Infect Control
  1991101-7.
• Revisiting the McGeer Criteria.
• Surveillance Definitions of Infections in Long
  Term Care Facilities.
• SHEA/CDC Position Paper.
• Stone N. Infection Control Hosp Epidemiol.
• 201233965-77.

10
Revised McGeer Criteria

• Focus was to increase the specificity and PPV of
  the criteria to limit unnecessary interventions
  and curb misallocation of scarce resources.
• Will be less sensitive than clinical diagnoses.
• Revised criteria provide explicit definitions for
  fever, acute confusion or altered mental status
  and acute functional decline.
• Attempt to harmonize the definitions used in
  acute and LTCFs (using gt 2 days at the facility
  to define a HAI).

11
Revised McGeer Criteria

• Criteria for systemic infections, common cold,
  conjunctivitis, ear infections, herpes simplex
  and zoster were left unchanged.
• Influenza was modified only to track cases
  outside the influenza season, as a consequence of
  pandemic H1N1.
• Criteria for gastrointestinal infections were
  unchanged, but specific criteria for norovirus
  and C. difficile were added.
• Skin infection criteria were not substantially
  changed, but NHSN criteria for surgical site
  infections was added.

12
Revised McGeer Criteria

• Major changes were made to the criteria for
  defining respiratory track and UTIs.
• Original McGeer criteria did not include a
  positive urine culture to define a UTI.
• More than half of residents suspected of having a
  UTI have negative cultures despite the high
  prevalence of asymptomatic bacteriuria.
• Juthani-Mehta M. J Am Geriatric Soc
  2007551072-7.

13
Revised McGeer Criteria

• Urinary tract symptoms alone are not sufficient
  to identify cases of UTI with a high level of
  specificity.
• Revised criteria require a positive urine culture
  as a necessary condition to diagnose a UTI.

14
Revised McGeer Criteria

• Define which infections should have priority in
  LTCF infection control, either because they are
  avoidable or cause significant morbidity and
  mortality.
• Priorities include
• Viral respiratory, GI and conjunctivitis due to
  high transmissibility.
• UTI, pneumonia, GI infections, SSTI (morbidity).
• Infections that can lead to serious outbreaks
  (hepatitis, norovirus, scabies, influenza, group
  A streptococci). Even a single case should
  trigger a more intensive investigation.

15
HBV and Glucose Monitoring

• 8 residents hospitalized, 6 died of acute HBV in
  a North Carolina assisted-living facility in 2010
  related to facility staff assisting with blood
  glucose monitoring.
• 16 outbreaks of HBV have been reported related to
  sharing of glucose monitoring equipment in
  assisted-living facilities since 2004.
• Moore Z. MMWR 201160182

16
HBV and Glucose Monitoring

• VDH was notified of acute HBV infections in
  residents from 4 assisted living facilities
  regulated by state agencies (not CMS) between
  2/2009 and 11/2011.
• All infections were among residents receiving
  assisted monitoring of blood glucose (AMBG).
• Attack rates by facility among susceptible
  residents receiving AMBG ranged from 17-92.
• AMBG has been responsible for 27 of 29 (93) HBV
  outbreaks in LTCFs since 1996.
• MMWR 201261339.

17
HBV and Glucose Monitoring

• 3 of 4 facilities had lapses in infection
  prevention practices
• Shared use of penlet-style reusable finger stick
  devices (intended only for a single patient).
• Failure to clean and disinfect shared
  glucometers.
• Poor hand hygiene techniques.

18
Diabetes and HBV

• 10/2011 ACIP recommended that adults 19-59 y.o.
  be vaccinated against HBV.
• Adults gt59 y.o. with DM may be vaccinated at the
  discretion of their physician.

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Blood Glucose Meters

• Whenever possible, blood glucose meters should
  not be shared.
• If they must be shared, the device should be
  cleaned and disinfected after every use, per
  manufacturers instructions.
• If the manufacturer does not specify how the
  device should be cleaned and disinfected then it
  should not be shared.

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Fingerstick Devices

• Fingerstick devices should never be used for more
  than one person.
• Single-use, auto-disabling fingerstick devices
  These are devices that are disposable and prevent
  reuse through an auto-disabling feature.
• In settings where assisted monitoring of blood
  glucose is performed, single-use, auto-disabling
  fingerstick devices should be used.

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Insulin Pens

• Insulin pens containing multiple doses of insulin
  are meant for use on a single person only, and
  should never be used for more than one person,
  even when the needle is changed.
• Insulin pens should be clearly labeled with the
  persons name or other identifying information to
  ensure that the correct pen is used only on the
  correct individual.

25
Insulin Pens

• Hospitals and other facilities should review
  their policies and educate their staff regarding
  safe use of insulin pens and similar devices.
• If reuse is identified, exposed persons should be
  promptly notified and offered appropriate
  follow-up, including bloodborne pathogen testing.
  

26
http//www.cdc.gov/nhsn/LTC/index.html

• CDCs National Healthcare Safety Network (NHSN)
  web site provides LTCFs a customized system to
  track infections in a streamlined and systematic
  way. Site provides NHSN enrollment, forms,
  toolkits, protocols and training to report C.
  difficile, MRSA and other drug-resistant
  infections, UTIs, and prevention process
  measures, including hand hygiene adherence.

27
UTI

1. New Case surveillance definition.
2. Who to treat

28
New UTI Surveillance Definition

• For residents without an indwelling catheter
  (both criteria
• 1 and 2 must be present).
• Criteria 1 At least 1 of the following sign or
  symptom
• Acute dysuria or acute pain, swelling, or
  tenderness of the testes, epididymis, or
  prostate.
• Fever or leukocytosis and at least 1 of the
  following localizing urinary tract symptoms (must
  be new or marked increase) acute costovertebral
  angle pain or tenderness, suprapubic pain, gross
  hematuria, incontinence, urgency, frequency.

29
UTI Surveillance Definition

• In the absence of fever or leukocytosis, then 2
  or more of the following localizing urinary tract
  symptoms
• Suprapubic pain
• Gross hematuria
• New or marked increase in incontinence
• New or marked increase in urgency
• New or marked increase in frequency

30
UTI Surveillance Definition

• Criteria 2. One of the following microbiologic
  subcriteria
• At least 100,000 cfu/mL of no more than 2 species
  of microorganisms in a voided urine sample.
• At least 100 cfu/mL of any number of organisms in
  a specimen collected by in-and-out catheter
• Urine specimens for culture should be processed
  as soon as possible, preferably within 12 h.
• If urine specimens cannot be processed within 30
  min of collection, they should be refrigerated.
  Refrigerated specimens should be cultured within
  24 h.

31
UTI Surveillance Definition

• UTI should be diagnosed when there are localizing
  genitourinary signs and symptoms and a positive
  urine
• culture result.
• A diagnosis of UTI can be made without localizing
  symptoms if a blood culture isolate is the same
  as the organism isolated from the urine and there
  is no alternate site of infection.

32
UTI Surveillance Definition

• In the absence of a clear alternate source of
  infection, fever or rigors with a positive urine
  culture result in the noncatheterized resident or
  acute confusion in the catheterized resident will
  often be treated as UTI.
• However, evidence suggests that most of these
  episodes are likely not due to infection of a
  urinary source.

33
UTI Surveillance Definition

• For residents with an indwelling catheter (both
  criteria 1
• and 2 must be present)
• Criteria1 (at least 1 of the following
  signs/symptoms)
• Fever, rigors, or new-onset hypotension, with no
  alternate site of infection.
• Either acute change in mental status or acute
  functional decline, with no alternate diagnosis
  and leukocytosis.
• New-onset suprapubic pain or costovertebral angle
  pain or tenderness.
• Purulent discharge from around the catheter or
  acute pain, swelling, or tenderness of the
  testes, epididymis, or prostate

34
UTI Surveillance Definition

• Criteria 2. Urinary catheter specimen culture
  with at least
• 100,000 cfu/mL of any organism(s).
• Recent catheter trauma, catheter obstruction, or
  new onset hematuria are useful localizing signs
  that are c/w UTI but are not necessary for
  diagnosis.
• Urinary catheter specimens for culture should be
  collected following replacement of the catheter
  (if current catheter has been in place for gt14 d).

35
UTI Surveillance Definition

• Pyuria (gt/ 10 WBC/hpf) does not differentiate
  symptomatic UTI from asymptomatic bacteriuria.
• Absence of pyuria in diagnostic tests excludes
  symptomatic UTI in residents of long-term care
  facilities.

36
Acute Functional Decline

• A new 3-point increase in total ADL score (range,
  028) from baseline, based on the following 7 ADL
  items, each scored from 0 (independent) to 4
  (total dependence)
• Bed mobility
• Transfer
• Locomotion within LTCF
• Dressing
• Toilet use
• Personal hygiene
• Eating

37
Acute Change in Mental Status

• Acute change in mental status from baseline (all
  criteria must be present)
• Acute onset.
• Fluctuating course.
• Inattention.
• AND
• Either disorganized thinking or altered level of
  consciousness.

38
Confusion Assessment Method Criteria

• Acute change in residents mental status from
  baseline
• Fluctuating Behavior coming and going or
  changing in severity during the assessment.
• Inattention difficulty focusing attention (eg,
  unable to keep track of discussion or easily
  distracted).
• Disorganized thinking thinking is incoherent
  (rambling conversation, unclear flow of ideas,
  unpredictable switches in subject).
• Altered level of consciousness level of
  consciousness is described as different from
  baseline (hyperalert, sleepy, drowsy, difficult
  to arouse, nonresponsive).

39
Treating Asymptomatic Bacteriuria

• Prospective randomized trials of screening for or
  treating asymptomatic bacteriuria have shown
• No decrease in the rate of symptomatic infection.
• No improvement in survival.
• No change in chronic genitourinary symptoms.
• Nicolle L. Am J Med
  19878327-33.
• Nicolle L. NEJM
  19833091420-5.
• Abrutyn E. Ann Intern Med
  1994120827-33.

40
Asymptomatic UTI Nursing Home

• 172 nursing home residents with an abnormal
  urinalysis and no Foley catheter.
• 146 did not meet criteria for treatment, 76 were
  not treated.
• None developed adverse consequences.
• No deaths or hospitalizations attributed to
  worsening infection or sepsis occurred during the
  following 3 months.
• Rotjanapan P. Arch Int Med
  2011171438-43.

41
Chronic Incontinence Ouslander et
al Ann Int Med 122 753
Randomized, placebo controlled trial of
antibiotic therapy
42
Detrimental Effects of Treating Asymptomatic UTI

• By 6-8 weeks after treating asymptomatic patients
  with bacteriuria, 60-80 will have recurrence
  with the same or a new infecting organism.
• Subjects who receive antimicrobial therapy for
  asymptomatic bacteriuria have
• Increased frequency of adverse events from the
  antibiotics.
• Increased reinfection with resistant organisms.
• Increased cost.

43
UTI and C. difficile

• 172 nursing home residents with an abnormal
  urinalysis and no Foley catheter.
• 85 did not meet criteria for treatment, but 41
  of them were started on antibiotics.
• 12 who received inappropriate antibiotics
  developed C. difficile infection within 3 weeks.
• Overall, those who received inappropriate
  antibiotics were 8-fold more likely to develop C.
  difficile within 3 months.
• Rotjanapan P. Arch Int Med
  2011171438-43.

44
Antibiotics and Warfarin

• Exposure to any antibiotic within 15d increased
  the chance of bleeding with hospitaliztion by
  2-fold.
• Azoles (eg fluconazole) increased risk by
  4.5-fold, TMP SMZ 2.7, cephalosporins 2.5,
  penicillins 1.9, macrolides 1.9, quinolones 1.7.
• Interference with metabolism (azoles, TMP SMZ)
  and disruption of bacteria that synthesize Vit K.
• Monitor INR one week after starting antibiotics.
• Baillargeon J. Am J Med 2012125183-9.

45
Mortality, Elderly Men
NEJM, 1983
46
Asymptomatic Bacteriuric Elderly Women
Amer J Med, 1987
47
Residents with Chronic Catheterization

• Bacterial colonization of residents with chronic
  indwelling foley catheters approaches 100,
  usually with 2-5 different organisms.
• Indwelling catheters develop a biofilm on the
  interior of the catheters where the organisms
  reside.
• Urine cultures in chronically catheterized
  residents often reflect the bacteriology of the
  catheter biofilm not the bladder urine.

48
Treatment of Asymptomatic Bacteriuria in
Chronically Catheterized Residents

• Asymptomatic bacteriuria is universal in patients
  with long term indwelling catheters.
• Antimicrobial therapy will not prevent
  bacteriuria or symptomatic infection.
• Antimicrobial therapy will lead to side effects,
  increasing resistance and cost.
• Asymptomatic bacteriuria should not be treated.

49
How do I decide which resident to treat for
suspected UTI?
50
Is It a UTI ? No easy Answers.

• For residents of LTCFs without a foley, 25-50
  of women and 15-40 of men have significant
  bacteriuria, but no symptoms.
• At the same time, UTI is also the most common
  cause of bacteremia in LTCF residents.
• Common cause of transfer to acute care
  facilities.
• How do I separate the large number of
  asymptomatic patients with bacteria in their
  urine who dont need treatment from those with
  serious infections that need treatment?

51
Does Pyuria Help ?

• 90 of residents with asymptomatic bacteriuria
  will have white blood cells in their urine
  (pyuria).
• In fact, 30 of all residents without bacteriuria
  will have pyuria.
• High rates are related to genital, bladder,
  prostatic or renal inflammation, usually
  non-infectious.
• Absence of pyuria essentially excludes UTI, but
  the presence of white cells is not helpful.

52
Does Appearance or Smell Help ?

• Foul smelling and cloudy urine have been used in
  the past to help determine who to treat.
• Neither foul smell or cloudy urine have been
  clearly associated with symptomatic UTI.

53
Cloudy/Foul Smelling Urine

• Nursing staff observes change in appearance or
  smell of urine (develop order set/policy)
• Not an indication for urinalysis or culture if
  asymptomatic.
• Provide scheduled toileting q2-4 hours.
• Gently cleanse perineum once daily and after each
  episode of incontinence.
• Monitor closely for symptoms/change in mental
  status.
• Khandelwal C. Annals of Long Term Care
  20122023-9.

54
Fever and Asymptomatic Bacteriuria

• A common diagnostic dilemna is the presence of
  fever with no localizing findings in a resident
  with bacteriuria and pyuria.
• Only 10 of these episodes are attributable to a
  urinary source in residents who do not have an
  indwelling foley catheter.
• Orr P. Am J Med
  199610071-77.

55
Clinical Deterioration and UTI

• UTI has been used as an explanation for
  nonspecific symptoms, such as
• clinical deterioration
• UTI was a cause of clinical deterioration in only
  11 of episodes.
• If UTI was the cause, all were febrile.
• Berman P. Age Ageing
  198716201-7.

56
Acute Change in Function and UTIs

• An acute deterioration in stable chronic
  symptoms may indicate an acute infection.
  Multiple co-existing findings such as fever with
  hematuria are more likely to be from a urinary
  source.
• In someone with nonspecific symptoms such as a
  change in function or mental status, bacteriuria
  alone does not necessarily warrant antibiotic
  treatment.
• Although sepsis, including urosepsis, can cause
  dizziness or falling, there is not clear evidence
  linking bacteriuria or a localized UTI to an
  increased fall risk. F315

57
The Never Ending Dilemna

• Clinically, the health care provider is faced
  with a difficult dilemna
• Indwelling bladder catheters are the 1 risk for
  bacteremia in LTCFs, but
• Essentially all urine cultures will be positive
  in residents with chronic catheterization.

58
Who Do You Treat ?

• Urinalysis and urine culture are only really
  helpful if negative (excludes a UTI).
• Fever is the most frequent clinical presentation
  of UTI in the chronically catheterized resident.
• Catheter obstruction is often a precipitating
  event for fever and systemic infection.
• Fever with hematuria or catheter obstruction has
  a high probability of being from a urinary source.

59
F315

• Because many residents have chronic bacteriuria,
  the research-based literature suggests treating
  only symptomatic UTIs.
• Symptomatic UTIs are based on the following
  criteria

60
F315 Indications to Treat a UTI

• Residents without a catheter should have at least
  three of the following signs and symptoms
• Fever (increase of gt2 degrees F/ rectal T gt99.5
  F/single T gt100 F).
• New or increased burning, pain on urination,
  frequency or urgency.
• New flank or suprapubic pain/tenderness.
• Change in character of urine (new bloody urine,
  foul smell or amount of sediment) or lab report
  (new pyuria or microscopic hematuria).
• Worsening of mental or functional status
  (confusion, lethargy, unexplained falls, recent
  onset incontinence, decreased activity or
  appetite).

61
F315 Indications to Treat a UTI

• Residents with a catheter should have at least
  two of the following signs and symptom
• Fever or chills.
• New flank pain or suprapubic pain/tenderness.
• Change in character of urine.
• Worsening of mental status or function.
• Local findings such as obstruction, leakage or
  mucosal trauma (hematuria) may also be present.

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63
How should I treat?Remove the Foley
catheter?Which antibiotic?
64
Catheter Change in Suspected UTI

• If urine culture is obtained from the old
  catheter, culture is polymicrobial in 52 vs.
  only 11 after changing the catheter.
• Patients who had catheter changes responded
  faster to treatment and had a lower relapse rate
  at 28 days (11 vs 41).
• Raz R. J Urol
  20001641254-8.

65
Treatment of Symptomatic UTI

• When a patient has fever and the source is felt
  to be the urinary tract in a patient with a
  chronic Foley catheter, there is a more rapid
  response and a lower rate of recurrent symptoms
  if the Foley catheter is changed prior to
  initiation of antibiotics.
• Suggests removal of the biofilm laden catheter is
  beneficial.
• Raz R. J Urol
  20001641254-58.

66
Choosing Antibiotics for UTI

• Be aware of local antimicrobial sensitivity
  patterns.
• Balance efficacy and collateral damage
  (resistance, C. difficile, antibiotic side
  effects).
• Use of an antibiotic in the last 3-6 months
  increases the risk of resistance.
• For acute cystitis, avoid antibiotics with gt 20
  resistance
• For pyelonephritis, avoid antibiotics with gt10
  expected resistance.
• International Practice Guidelines for Rx of
  Uncomplicated Cystitis and Pyelonephritis.
  Clin Infect Dis 201152e103-e120.

67
Sentara Antimicrobial Resistance, 2011

• E. coli
  Resistance
• Ampicillin
  54 (40)
• Ciprofloxacin 34
  (7)
• TMP/SMX 28
  (21)
• Nitrofurantoin 7
  (0.5)
• Ceftriaxone
  7
• Zosyn
  7
• Gentamicin 12
• Meropenem 0
• 2010 E. coli resistance for urine isolates,
  16-45 yo U.S. women

68
Predicting Resistance

• 633 E. coli UTIs with 36 trimethoprim resistant
  and 12 ciprofloxacin resistant.
• Odds of resistance increased with each TMP
  prescription in the preceding year one Rx 1.4
  fold, two 5-fold, three or more 6-fold.
• Odds of resistance increased with each cipro
  prescription in the preceding year one Rx 3-
  fold, two or more 7-fold.
• Vellinga A. J Antimicrob Chemother June 2012.
  Epub

69
The More You Use It, The Faster You Lose It !
70

• International Clinical Practice Guidelines
• for the Treatment of
• Acute Cystitis and Pyelonephritis
• in Women
• Gupta K. Clin Infect Dis 201152e103-e120.
  

71
Antibiotics for UTI

• First-line therapy Cystitis/Bladder infection
• Nitrofurantoin (Macrodantin, Macrobid, Furadantin
  susp) 100 mg twice daily for 5 days.
• Common side effects N, V
• Rare acute, subacute chronic pulmonary reactions
  1 or less/100,000.
• Contraindicated for CrCl lt 60 (minimal levels in
  urine).
• Not used for pyelonephritis/possible urosepsis
  (low or undetectable serum levels).

72
Antibiotics for UTI

• Trimethoprim-sulfamethoxazole DS one 160 mg-800
  mg tablet twice daily for 3 days.
• One TMP 80 mg- SMZ 400 mg tablet twice daily for
  CrCl lt 30 not recommended for CrCl lt 15.
  (sulfamethoxazole may be subtherapeutic with
• CrCl lt 50).
• Trimethoprim 100 mg twice daily 100 mg every 18
  h for CrCl 30. (excellent levels in urine even
  with low CrCl).

73
Bactrim (TMP-SMZ) Resistance

• 104 women with a TMP-SMZ resistant isolate who
  were treated with TMP-SMZ vs. 33 with a sensitive
  isolate.
• Clinical success rate of TMP-SMZ was 54 if the
  isolate was resistant vs. 96 if the isolate was
  sensitive.
• Brown P. Clin Infect Dis
  2002341061-6.
• Urine concentrations of TMP are 100-fold higher
  than serum.

74
Fosfomycin (Monurol)

• Phosphonic acid antimicrobial, bactericidal,
  inhibits peptidogylcan synthesis disrupting cell
  wall.
• Available as 3 gm packet, mixed in water, 50.
• Very well tolerated, nausea is major side effect.
  
• Long half life, dosing q2-3d.
• Good tissue levels, excreted unchanged in urine,
  high levels in urine (100 ug for 48 hours).

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Fosfomycin (Monurol)

• Very broad spectrum VRE, MRSA, most GNR,
  including ESBL and KPC, but Pseudomonas and
  Acinetobacter usually resistant.
• Approved for treatment of uncomplicated UTI
  (single dose 3 gm).
• Off label use for complicated UTI (3 gm every 2-3
  days x 3 doses), prostatitis (3 gm q3d x 21
  days).

76
Antibiotics for UTI

• Alternatives More resistance and collateral
  damage (C. difficle, MRSA colonization).
• Ciprofloxacin hydrochloride 250 mg twice daily
  for 3 days 250 mg every 18 h for CrCl lt 30 250
  mg/d for CrCl lt 10.
• Levofloxacin 250 mg/d for 3 days 250 mg every 48
  h for CrCl lt 20.

77
Quinolone and Tendon Rupture

• 1,367 with achilles tendon rupture vs. 50,000
  controls.
• Risk increased 6.4-fold for 60-79 y.o. and
  20.4-fold for those gt 80 y.o. who used quinolones
  at a median of 7d.
• 2 - 6 of all achilles tendon ruptures in people
  gt 60 y.o. can be attributed to quinolones.
• Concomitant use of steroids significantly
  increased the risk in those gt 60 y.o. by 3-fold.
• Van der Linden P. Arch Int Med
  20031631801-7.

78
Quinolones and Retinal Detachment

• 4,384 cases of retinal detachment vs. 43,840
  controls who had visited an ophthalmologist.
• Current use of quinolones had a 4.5-fold
  increased risk of retinal detachment time to
  onset 5 days.
• No association with recent or past use.
• Absolute risk of 4 per 10,000 person years
  number needed to harm 2,500 for any use.
• Estimated 1,440 cases of retinal detachment in
  the U.S. annually from quinolone use.
• Etminan M. JAMA
  20123071414-19.

79
Quinolones and Hepatitis

• Trovafloxacin removed from the market for
  hepatotoxicity.
• 2009 European Medicines Agency called for
  restriction of moxifloxacin in rx of CAP 2010
  Health Canada released a warning for rare severe
  hepatotoxicity.
• Patients over 65 y.o. had a 2.2-fold and
  levofloxacin a 1.9-fold increased risk of
  admission for hepatotoxicity, 61 died during
  hospitalization. (8 cases/100K exposures).
• No increased risk for ciprofloxacin.
• Paterson J. CMAJ Aug
  2012.

80
Ciprofloxacin Resistance

• 87 adult patients with UTI with an organism
  resistant to ciprofloxacin who were treated with
  ciprofloxacin.
• 75 microbiologic cure, 77 clinical response.
• Pseudomonas had a lower response than other
  pathogens (46 vs. 82).
• Jeffries M. Ann Pharmacother
  201145824-25.
• Levels of ciprofloxacin in urine are 100X gt than
  serum.

81
Duration of Treatment

• Most experts recommend that antimicrobial
  treatment should be for as short a period as
  possible 5-7 days for catheter associated UTI.
• Rationale is to decrease emergence of resistance,
  but will also decrease cost.

82
Pyelonephritis

• Residents not requiring hospitalization
• Ciprofloxacin 500 mg bid x 7 days.
• If ciprofloxacin resistance exceeds 10, initial
  long acting parenteral antimicrobial (ceftriaxone
  1 gm or single daily dose aminoglycoside
  (gentamicin or tobramycin 4-7 mg/kg q24h).
• Tailor antibiotics according to sensitivity.
• Duration 10-14 days

83
Should I do a test of cure culture?
84
F315 Follow-Up of UTIs

• The goal of treating a UTI is to alleviate
  systemic or local symptoms, not to eradicate all
  bacteria. Therefore, a post-treatment culture is
  not routinely necessary but may be useful in
  certain situations.
• Continued bacteriuria without residual symptoms
  does not warrant repeat or continued antibiotic
  therapy.

85
Exception for Follow Up Culture

• If the resident is in contact isolation because
  of a resistant organism, such as an extended
  spectrum beta lactaamase (ESBL) producing E. coli
  or Klebsiella or another highly resistant gram
  negative rod (such as Acinetobacter), MRSA, or
  VRE, then a negative culture is required to
  remove them from contact isolation.
• If the repeat urine culture is positive,
  treatment is only indicated if the resident is
  symptomatic.
• Retreatment is not used to eradicate colonization
  or in an asymptomatic resident.

86
Clostridium difficile Infection

1. Surveillance definition
2. Diagnosis and treatment of infection

87
CDI and Health Care

• 300,000 annual cases of healthcare associated CDI
  each year at a cost of 3.2 billion.
• 20 of hospital onset CDI occurred in residents
  of nursing homes.
• 67 of nursing home onset CDI occurred in
  patients recently discharged from an acute care
  hospital.
• Antibiotic use increases the risk of CDI 10-fold
  while the patient is taking antibiotics and for
  one month after stopping and 3-fold for the next
  2 months.
• MMWR 201261157-62.

88
Clostridium difficile Infection

• Most common cause of hospital acquired diarrhea
  due to an infectious cause.
• 100 increase in cases and a 400 increase in
  mortality in the last decade.
• 90 of deaths are in persons gt 65 y.o.
• Redelings M. Emerg Infect Dis
  20071417-19.

89
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90
Epidemic C. difficile Strain

• Epidemic C. difficile strains have acquired
  resistance to fluoroquinolones.
• Ciprofloxacin was the antibiotic associated with
  the highest risk of developing CDI (3.4-fold).
• In Quebec, 55 of CDI patients had received a
  quinolone.
• Pepin J. Clin Infect Dis
  2005411254-60.

91
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92
CDI and PPIs

• Gastric acidity is natures disinfectant,
  killing vegetative C. difficile, Shigella,
  Salmonella and Vibrios.
• Dial found a strong association with PPI use (OR
  3.5) among outpatients, but none with H2 receptor
  antagonists. CMAJ 206175745-48.
• Lowe found no correlation with PPIs in
  hospitalized patients after adjusting for other
  medications and comorbidity. Clin Infect Dis
  2006431272-76.
• 2/2012 FDA safety notice on risk of CDI with
  PPIs.

93
CDI Surveillance Definition

• Clostridium difficile infection (both criteria 1
  and 2 must be present)
• Criteria1. One of the following.
• Diarrhea 3 or more liquid or watery stools above
  what is normal for the resident within a 24-h
  period.
• Presence of toxic megacolon (abnormal dilatation
  of the large bowel, documented radiologically).

94
CDI Surveillance Definition

• Criteria 2. One of the following
• Stool sample yields a positive laboratory test
  result for C. difficile toxin A or B, or a
  toxin-producing C. difficile organism is
  identified from a stool sample culture or by a
  molecular diagnostic test such as PCR.
• Pseudomembranous colitis is identified during
  endoscopic examination or surgery or in
  histopathologic examination of a biopsy specimen.

95
CDI Surveillance Definition

• Primary episode of C. difficile infection is
  defined as one that has occurred without any
  previous history of C. difficile infection.
• or has occurred gt 8 weeks after the onset of a
  previous episode of C. difficile infection.

96
CDI Surveillance Definition

• Recurrent episode of C. difficile infection is
  defined as an episode that occurs 8 wk or sooner
  after the onset of a previous episode, provided
  that the symptoms from the earlier (previous)
  episode have resolved.
• Individuals previously infected with C. difficile
  may continue to remain colonized even after
  symptoms resolve.

97
CDI Clinical

• Broad range from mild self limited diarrhea to
  colitis with or without pseudomembranes to
  fulminating colitis with toxic megacolon.
• Bloody diarrhea is uncommon (5-10) only 25
  have occult blood fecal leukocytes in 28-40.
• Fever is noted in 30-50 usually low but can be
  as high as 106 degrees F.

98
CDI Diagnosis

• Leukocytosis and hypoalbuminemia are very
  suggestive.
• In one study, the mean WBC with CDI was 15,800
  with 26 having a WBC gt20K and 6 gt30K.
• For all patients with WBC gt30,000 who do not have
  a hematologic malignancy, 25 have CDI.
• Wanahita A. Clin Infect Dis
  2002341585-92.

99
The Nose Knows

• Urban legend exists among nurses that they can
  accurately diagnose CDI on smell alone.
• Study of 138 nursing staff sensitivity was 55,
  but NPV was 92 overall accuracy was 79.
• Nurses were able to exclude a diagnosis of CDI
  with a high degree of confidence and accuracy.
• Burdette S. CID 2007441142.
  
• May lead to a new certification AOCDCRN
• (advanced olfactory C. difficile certified
  RN)

100
CDI EIA

• Enzyme immunoassay for C. difficile toxin is
  rapid and less expensive than other tests.
• Reported sensitivity is 75-85 (in a study from
  Johns Hopkins, sensitivity was only 40).
• Test only on specimens that take the shape of the
  container 13 of liquid specimens were toxin
  (), 17 of soft were ().

101
C. Diff x 3 Dont Do It

• Repeated assays may account for 36 of all tests
  ordered, but only 1 of positive assays.
• Renshaw A. Arch Pathol Lab Med
  199612049-52.
• Repeat assays represented 17 of all assays, only
  1 () at a cost of 128/assay.
• Mohan S. Am J Med
  2006119356.E7.

102
EIA Repeat Testing

• Testing 1,000 patients with prevalence of 10 and
  sensitivity of 73, specificity 98.
• True Positive False Positive
  Undetected
• First 73 24
  27
• Second 18 9
  9
• Third 7 21
  2
• Peterson L. Ann Intern Med
  2009151176-9.

103
CDI EIA

• No indication for serial monitoring or
  end-of-treatment-test-of-cure 1/3 have a
  positive toxin assay at the end of successful
  treatment.
• Bartlett J. NEJM
  2002346334-9.
• Stool carriage may persist for 3-6 weeks after
  successful treatment and has not been found to
  predict relapse.
• Issack M. Lancet
  1990335610-11.

104
CDI Treatment Basics

• Stop the offending antibiotic.
• Up to 25 will resolve spontaneously, observation
  alone may be adequate.
• If antibiotics can not be stopped, change to
  lower risk antibiotics. (aminoglycosides,
  sulfonamides, macrolides, and tetracyclines).
• Avoid antimotility agents.
• Novak E. JAMA
  19762351451-4.
• Opiates may prevent diarrhea, obscuring the
  diagnosis.

105
Metronidazole vs. Vancomycin

• Metronidazole has been the preferred drug because
  of risk of VRE and the cost.
• No patients developed VRE in a study of 20
  patients treated with oral vancomycin.
• Selgado, C. Infect Control Hosp Epidemiol
  200425413-17.
• .But vancomycin capsules 125 mg qid are 36.80
  each AWP (60-120/day retail) vs. 2.19/day for
  metronidazole 500 mg tid. (most facilities use
  the intravenous powder compounded in a flavored
  solution lt 5.00/day).

106
CDI Vancomycin

• Vancomycin has been called a pharmacologic
  dream.
• You put it in the mouth and it all winds up in
  the colon.
• Very minimal absorption with stool levels of
  gt1000 ug/ml, which exceeds the MIC by 1000-fold.
• Cure rates have been 86-99 relapse rates of
  15-33.
• Dose of 125 mg qid po has been shown to be as
  effective as 500 mg qid.
• Reserved for metronidazole failures (no response
  at 3-5 days) or severe CDI.

107
SHEA/IDSA Guidelines for CDI

• Mild Moderate WBC lt15,000 lt 50 increase in
  Cr from baseline.
• Severe WBC gt/ 15,000 or 50 increase of Cr
  from baseline.
• Severe complicated severe disease plus ICU
  admission, need for colectomy, ileus, toxic
  megacolon, hypotension, colonic perforation.
• Cohen S. Infect Control Hosp Epidemiol.
  201031431-55.

108
CDI Treatment

• Mild Moderate oral metronidazole 500 mg tid.
• Severe oral vancomycin 125 mg qid
• Severe complicated high dose oral vancomycin 500
  mg qid by nasogastric tube if necessary and/or
  metronidazole IV 500 750 mg q8h.
• For complete ileus, IV metronidazole plus
  vancomycin by retention enema.

109
Fidaxomicin

• Fidaxomycin is a macrocyclic antibiotic with
  minimal absorption and high fecal levels.
• Bactericidal against C. difficile and 8-fold
  more active than vancomycin, which is
  bacteriostatic.
• Minimal activity against fecal flora, especially
  Bacteroides sp., while vancomycin has significant
  activity against Bacteroides sp.

110
Fidaxomicin

• Randomized to fidaxomicin vs. vancomycin with 92
  vs. 90 clinical cure.
• Recurrence of infection was 15 for fidaxomicin
  vs. 25 for vancomycin, overall.
• No difference in recurrence with epidemic strain,
  but for the 64 of patients with other strains
  there was a 69 reduction in recurrence.
• Louie T. NEJM 2011364422-31.

111
Cost of CDI agents

• Fidaxomicin 200 mg bid 140./dose
• 
  2,800. for 10d
• Metronidazole 500 mg tid .20/dose
• 
  6 for 10d
• Vancomycin caps 125 mg qid 30.00/dose
• 
  1,273. for 10d
• Vancomycin injection given po 1.68/dose
• 
  67. for 10d

112
CDI Relapse

• Recurrence after initial resolution of symptoms
  occurs in 20-25 after initial episode, usually
  within 5-8 days, but may be delayed for weeks to
  years.
• Risk for recurrence gt 65 y.o., comorbidities,
  another antibiotic course, prior recurrence (up
  to 45 risk).

113
Early Preventative Therapy

• Treatment of persons known to be colonized or a
  recent episode of CDI who require antibiotic
  treatment.
• Despite the absence of guidelines for this
  approach, there is remarkable homogeneity in that
  clinicians who practice this prophylactic
  strategy use oral metronidazole or vancomycin
  during the entire course of antimicrobial therapy
  and for an additional 7 days after the end of its
  administration.
• Miller M. Clin Infect Dis
  200745S122-8.

114
CDI Relapse

• First recurrence Repeat a course of the initial
  antibiotic used, usually metronidazole.
• Second or more vancomycin preferred (not
  absorbed, high stool levels) over metronidazole
  (readily absorbed, stool levels decrease with
  decreasing inflammation, undetectable when
  diarrhea resolves).
• Vancomycin often tapered and pulsed.

115
CDI Relapse

• Oral vancomycin with taper and pulsed dosing at
  125 mg qid for 7 days, tapering to bid for 7
  days then daily for 7 days. Tedesco F. Am J
  Gastro 198580867-8.
• Followed by pulsed dosing, which allows for
  germination of residual spores during days off,
  followed by killing of the vegetative form when
  vancomycin is given again.
• Give vancomycin 250 mg every 2-3 days for 3
  weeks others gradually lengthen pulsing interval
  to once every 10 days. Surawicz C. Nat Clin Pract
  Gastro Hepatol 2004132-8.

116
Probiotic Problems

• High of patients receiving antibiotics (2/3)
• (can not use vancomycin rapidly kills
  Lactobacilli)
• Doses and products vary results are specific to
  species and number of viable cells.
• Maximum viable cells at end of manufacture
  minimum number at end of shelf life, number that
  transit to colon differ.

117
Probiotics Saccharomyces

• McFarland in a double-blind, randomized, placebo
  controlled trial of S. boulardii found no
  decrease in initial recurrence, but found a 50
  reduction in further recurrences (35 vs. 65, p
  0.04).
• McFarland L. JAMA 19942711913-18.
• Surawicz conducted a second study with S.
  boulardii which confirmed a decrease in
  recurrences only with high dose vancomycin (500
  mg qid), but no effect with metronidazole or
  vancomycin 125 mg qid.
• Surawicz C. Clin Infect Dis
  2000311012-17.

118
CDI Recurrences

• Stool transplantation from a donor administered
  via nasogastric tube or colonoscope.
• Donor usually spouse.
• Lacks aesthetic appeal, but appears to be highly
  effective (92).
• Toying with Human
  Motions
• Borody T. J Clin Gastroenterol
  200438475-83.

119
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120
CDI Prevention

• Numerous hospital and nursing home outbreaks have
  been reported. Johnson S. NEJM
  19993411645-51.
• C. difficile spores can persist in the
  environment for months on floors, bedding and
  furniture.
• 59 of HCW caring for patients with CDI had C.
  difficile cultured from their hands, including
  75 of physicians. McFarland L. NEJM
  1989320204-10.

121
CDI Prevention

• Private room in contact isolation or cohort.
• Gloves have been clearly shown to decrease
  acquisition of C. difficile by HCW and decrease
  the incidence of CDI. Johnson S. Am J Med
  199088137-40.
• Avoid rectal thermometers.
• Neither soap water or alcohol products can kill
  the spore form of C. difficile, but soap water
  can remove the spores from the hands.
• Most effective surface cleaning is with bleach.

122
Bleach Decontamination

• Decontamination with a bleach spray with 500 ppm
  resulted in a 79 reduction in the number of ()
  surface cultures. Katz G. Am J Epidemiol
  19881271289-94.
• Switch from a quarternary ammonium to a 110
  hypochorite solution for disinfection of rooms
  for patients with CDI resulted in a 63 reduction
  in CDI cases. Mayfield J. Clin Infect
  Dis 200031995-1000.
• Figueroa reported a 68 decrease in HCA CDI,
  despite stable CDI admission rates, after change
  to a universal bleach-based cleaning protocol was
  introduced for all hospital discharges.
  45th IDSA Oct 2007. Ab3 LB-6

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124
MRSA
125
CA MRSA

• gt80 of all SSTIs are caused by MRSA.
• Most spider bites are MRSA.
• Incision and drainage (ID) alone may be adequate
  for uncomplicated abscesses.
• Antibiotics alone are not adequate for fluctuant
  abscesses.
• For patients with suspected CA MRSA, it is
  important to obtain specimens for culture and
  sensitivity (CS).

126
CA MRSA and Antibiotics

• 531 episodes of CA MRSA SSTI, 75 abscesses.
• 8 had treatment failure (repeat ID, new abscess
  while on Rx, hospitalization).
• Failure to start active antibiotic within 48
  hours of initial ID was the only variable
  associated with treatment failure (OR 2.8) or 95
  vs. 87 success.
• Ruhe J. Clin Infect Dis
  200744777-84.

127
CA MRSA Treatment

• Trimethoprim-sulfamethoxazole (Septra, Bactrim)
  is a reasonable choice.
• Can add rifampin 300 mg bid or 600 mg qd, but
  never use rifampin alone (rapid resistance).
• If ciprofloxacin or another quinolone is used,
  combine with rifampin to prevent the emergence of
  resistance.
• Doxycycline or minocycline may be of value.
• Medical Letter
  20064813-4.

128
MRSA Colonization in LTCF

• Point prevalence studies in VA units found 25-35
  of residents are positive at any given time.
• In areas where MRSA is common, 9-12 of residents
  in free standing LTCF are colonized.
• 65 are colonized for a long time, the remainder
  have transient colonization.

129
MRSA and the LTCF

• Patients generally acquire MRSA in the acute care
  facility.
• Transmission from resident to resident in the
  LTCF is infrequent, although occasional outbreaks
  have been described.
• Environmental cultures from common areas are
  seldom positive, although the residents immediate
  environment is commonly positive.
• Prevalence of colonization may be high, but
  infection is uncommon.

130
Frequency of MRSA Colonization at Various
Patient Body Sites
Forehead 51 Nose 54 -
93 Neck 35 Axilla
13 - 28 Hands 40 Groin
30 - 39
95 of nasal carriers had MRSA at
extranasal sites
Hill RLR et al. JAC 198822377 Sanford MD et al.
CID 1994
Rohr U et al. Int J Hyg Environ Health
200420751
131
MRSA and Isolation

• Most Desirable Private room or cohorting with
  another person who is colonized with MRSA.
• Less Desirable Room with a resident who has
  intact skin and no tubes (PEG, trach, IV,
  foley).
• Should not be placed with resident who has
  another resistant organism (i.e. VRE).

132
MRSA Colonization and Activities

• Resident may attend activities as long as
• Any colonized or infected site can be securely
  covered.
• Resident can observe acceptable hygiene and wash
  his/her hands.
• Resident with MRSA in sputum does not need to
  wear a mask if he/she can cover mouth and nose
  with tissue when coughing.
• Resident who cannot control secretions should not
  attend group activities.

133
MRSA and the LTCF

• Intensive barrier and isolation precautions have
  not been shown to be more beneficial than gloving
  and hand washing.
• Decolonization efforts are usually ineffective
  and have not decreased infections.
• Generalized screening is not justified.
• No evidence to support non-admission of patients
  from acute care facilities.

134
MRSA Infection Control

• Staff should use Contact Precautions
• Handwashing After removing gloves, before
  leaving the room.
• Gloves When physical contact with resident is
  anticipated.
• Gowns Substantial contact of clothes with
  patient or environmental surfaces or ileostomy,
  colostomy, diarrhea, incontinence, or wound
  drainage that is not contained.
• Masks When splashes possible (suctioning/irrigati
  on).
• No special cleaning of rooms required.

135
MRSA and LTCF

• LTCF should not refuse placement if room
  available (single, cohort or low risk resident).
• Leads to overuse of hospital resources and a
  false sense of security for LTCF management.
• MRSA patients in hospitals or LTCF do not need
  two negative cultures for MRSA prior to transfer,
  decolonization prior to transfer should not be
  required.
• Inform hospitals or other LTCF of MRSA status on
  transfer.

136
Termination of Isolation at the LTCF

• 2 cultures of colonized or infected site are
  negative, one week apart.
• First culture should be taken at least 72 hours
  after antibiotic treatment has been stopped.
• If sputum cannot be obtained, throat swab may be
  used.
• If wound is healed, healed site may be cultured
  with moist swab.

137
Nares Cultures

• Do not obtain nares cultures when obtaining
  cultures at other body sites.
• Nares cultures are not needed to discontinue
  contact precautions.
• Nares cultures only used if resident is
  implicated in MRSA outbreak.
• Decolonization of nares is not routinely
  indicated.

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139
Metronidazole vs. Vancomycin

• First randomized, double-blind, placebo
  controlled trial of metronidazole vs. vancomycin.
• Stratified by Scoring System at study entry into
  mild and severe disease.
• Zar F. Clin Infect Dis
  200745302-7.

140
CDI Severity Scoring System

• 
  Points
• Age gt 60 y.o.
  1
• Temp gt 38.3 C 1
• Albumin lt 2.5 mg/dl 1
• WBC gt 15,000 1
• Rx in ICU
  2
• Pseudomembranes 2
• Mild 0-1, Severe 2 or more.

141
CDI Outcomes Clinical Cure

• Metronidazole
  Vancomycin
• Mild CDI 90
  98
• Severe CDI 76
  97
• Recurrences 15
  14