Transcript UTI and C. DIfficile Infection - Virginia Medial Director`s Association

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
Ageing Population
• By 2030, 20% of the U.S. population will be over 65
years old.
• Currently, > 16,000 nursing homes/LTCFs with 1.5
million residents in the U.S.
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.
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 1991;39:963-72.
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. 2012;33:978-80.
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.
“The Perfect Storm of
Antimicrobial Resistance”
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.
Mc Geer Criteria. Definitions of Infections in
Long Term Care Facilities. Am J Infect Control
1991;10:1-7.
Revisiting the McGeer Criteria.
Surveillance Definitions of Infections in Long
Term Care Facilities.
SHEA/CDC Position Paper.
Stone N. Infection Control Hosp Epidemiol.
2012;33:965-77.
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 > 2 days at the facility to define a HAI).
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.
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 2007;55:1072-7.
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.
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.
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 assistedliving facilities since 2004.
Moore Z. MMWR 2011;60:182
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 2012;61:339.
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.
Diabetes and HBV
• 10/2011: ACIP recommended that adults 19-59 y.o. be
vaccinated against HBV.
• Adults >59 y.o. with DM may be vaccinated at the
discretion of their physician.
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 manufacturer’s
instructions.
• If the manufacturer does not specify how the device
should be cleaned and disinfected then it should not be
shared.
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.
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 person’s
name or other identifying information to ensure that the
correct pen is used only on the correct individual.
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.
http://www.cdc.gov/nhsn/LTC/index.html
CDC’s 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.
UTI
A. New Case surveillance definition.
B. Who to treat
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.
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
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 1–2 h.
• If urine specimens cannot be processed within 30 min of
collection, they should be refrigerated. Refrigerated
specimens should be cultured within 24 h.
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.
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.
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
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 >14 d).
UTI Surveillance Definition
• Pyuria (>/= 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.
Acute Functional Decline
A new 3-point increase in total ADL score (range, 0–28)
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
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.
Confusion Assessment Method Criteria
Acute change in resident’s 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).
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 1987;83:27-33.
Nicolle L. NEJM 1983;309:1420-5.
Abrutyn E. Ann Intern Med 1994:120:827-33.
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 2011;171:438-43.
Chronic Incontinence
Ouslander et al Ann Int Med 122: 753
Randomized, placebo controlled trial of antibiotic therapy
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.
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 2011;171:438-43.
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 2012;125:183-9.
Mortality, Elderly Men
NEJM, 1983
Asymptomatic Bacteriuric: Elderly Women
Amer J Med, 1987
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.
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.
How do I decide which resident to
treat for suspected UTI?
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 don’t need
treatment from those with serious infections that need
treatment?
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.
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.
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 2012;20:23-9.
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 1996;100:71-77.
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 1987;16:201-7.
Acute Change in Function and UTI’s
• “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
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.
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.
F315
• “Because many residents have chronic
bacteriuria, the research-based literature suggests
treating only symptomatic UTIs.
• Symptomatic UTIs are based on the following
criteria:
F315: Indications to Treat a UTI
Residents without a catheter should have at least three of
the following signs and symptoms:
• Fever (increase of >2 degrees F/ rectal T >99.5 F/single T >100 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).
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.
How should I treat?
Remove the Foley catheter?
Which antibiotic?
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 2000;164:1254-8.
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 2000;164:1254-58.
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 > 20% resistance
• For pyelonephritis, avoid antibiotics with >10% expected
resistance.
International Practice Guidelines for Rx of Uncomplicated Cystitis
and Pyelonephritis. Clin Infect Dis 2011;52:e103-e120.
Sentara Antimicrobial Resistance, 2011
E. coli
Resistance
•
•
•
•
•
•
•
•
54% (40)*
34% (7)
28% (21)
7% (0.5)
7%
7%
12%
0
Ampicillin
Ciprofloxacin
TMP/SMX
Nitrofurantoin
Ceftriaxone
Zosyn
Gentamicin
Meropenem
*2010 % E. coli resistance for urine isolates, 16-45 yo U.S. women
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
The More You Use It,
The Faster You Lose It !
69
International Clinical Practice Guidelines
for the Treatment of
Acute Cystitis and Pyelonephritis
in Women
Gupta K. Clin Infect Dis 2011;52:e103-e120.
70
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 < 60 (minimal levels in urine).
• Not used for pyelonephritis/possible urosepsis (low or
undetectable serum levels).
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 < 30; not recommended for CrCl < 15.
(sulfamethoxazole may be subtherapeutic with
CrCl < 50).
• Trimethoprim 100 mg twice daily; 100 mg every 18 h for
CrCl 30. (excellent levels in urine even with low CrCl).
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 2002;34:1061-6.
• Urine concentrations of TMP are 100-fold higher than
serum.
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).
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).
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 < 30; 250 mg/d for
CrCl < 10.
• Levofloxacin 250 mg/d for 3 days; 250 mg every 48 h for
CrCl < 20.
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 > 80 y.o. who used quinolones at a median of 7d.
• 2 - 6% of all achilles tendon ruptures in people > 60 y.o.
can be attributed to quinolones.
• Concomitant use of steroids significantly increased the
risk in those > 60 y.o. by ~3-fold.
Van der Linden P. Arch Int Med 2003;163:1801-7.
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 2012;307:1414-19.
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.
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 2011;45:824-25.
• Levels of ciprofloxacin in urine are 100X > than serum.
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.
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
Should I do a test of cure culture?
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 posttreatment 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.”
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.
Clostridium difficile Infection
1. Surveillance definition
2. Diagnosis and treatment of infection
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 2012;61:157-62.
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 > 65 y.o.
Redelings M. Emerg Infect Dis 2007;1417-19.
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 2005;41:1254-60.
CDI and PPIs
• Gastric acidity is “nature’s 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 206;175:745-48.
• Lowe found no correlation with PPIs in hospitalized
patients after adjusting for other medications and
comorbidity. Clin Infect Dis 2006;43:1272-76.
• 2/2012: FDA safety notice on risk of CDI with PPIs.
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).
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.
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 > 8 weeks after the onset of a previous
episode of C. difficile infection.
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.
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.
CDI: Diagnosis
• Leukocytosis and hypoalbuminemia are very suggestive.
• In one study, the mean WBC with CDI was 15,800 with
26% having a WBC >20K and 6% >30K.
• For all patients with WBC >30,000 who do not have a
hematologic malignancy, 25% have CDI.
Wanahita A. Clin Infect Dis 2002;34:1585-92.
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 2007;44:1142.
• May lead to a new certification: AOCDCRN
(advanced olfactory C. difficile certified RN)
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 (+).
C. Diff x 3: Don’t Do It
• Repeated assays may account for 36% of all tests
ordered, but only 1% of positive assays.
Renshaw A. Arch Pathol Lab Med 1996;120:49-52.
• Repeat assays represented 17% of all assays, only 1% (+)
at a cost of $128/assay.
Mohan S. Am J Med 2006;119;356.E7.
EIA: Repeat Testing
• Testing 1,000 patients with prevalence of 10% and
sensitivity of 73%, specificity 98%.
True Positive False Positive Undetected
First
Second
Third
73
18
7
24
9
21
27
9
2
Peterson L. Ann Intern Med 2009;151;176-9.
CDI: EIA
• No indication for serial monitoring or end-of-treatmenttest-of-cure; 1/3 have a positive toxin assay at the end of
successful treatment.
Bartlett J. NEJM 2002;346:334-9.
• Stool carriage may persist for 3-6 weeks after successful
treatment and has not been found to predict relapse.
Issack M. Lancet 1990;335:610-11.
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 1976;235:1451-4.
• Opiates may prevent diarrhea, obscuring the diagnosis.
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 2004;25:413-17.
• ….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;
< $5.00/day).
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 >1000
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.
SHEA/IDSA Guidelines for CDI
• Mild – Moderate: WBC <15,000; < 50% increase in Cr
from baseline.
• Severe: WBC >/= 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. 2010;31:431-55.
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.
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.
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 2011;364:422-31.
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
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: > 65 y.o., comorbidities, another
antibiotic course, prior recurrence (up to 45% risk).
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 2007;45:S122-8.
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.
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 1985;80:867-8.
• 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 2004;1:32-8.
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.
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 1994;271:1913-18.
• 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 2000;31:1012-17.
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 2004;38:475-83.
CDI: Prevention
• Numerous hospital and nursing home outbreaks have
been reported. Johnson S. NEJM 1999;341:1645-51.
• 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 1989;320:204-10.
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 1990;88:137-40.
• 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.
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 1988;127:1289-94.
• Switch from a quarternary ammonium to a 1:10
hypochorite solution for disinfection of rooms for
patients with CDI resulted in a 63% reduction in CDI
cases.
Mayfield J. Clin Infect Dis 2000;31:995-1000.
• 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
MRSA
CA MRSA
• >80% of all SSTIs are caused by MRSA.
• Most “spider bites” are MRSA.
• Incision and drainage (I&D) 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 (C&S).
CA MRSA and Antibiotics
• 531 episodes of CA MRSA SSTI, 75% abscesses.
• 8% had treatment failure (repeat I&D, new abscess while
on Rx, hospitalization).
• Failure to start active antibiotic within 48 hours of initial
I&D was the only variable associated with treatment
failure (OR 2.8) or 95% vs. 87% success.
Ruhe J. Clin Infect Dis 2007;44:777-84.
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 2006;48:13-4.
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.
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.
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 1988;22:377
Sanford MD et al. CID 1994
Rohr U et al. Int J Hyg Environ Health 2004;207;51
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).
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.
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.
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/irrigation).
– No special cleaning of rooms required.
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.
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.
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.
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 2007;45:302-7.
CDI Severity Scoring System
•
•
•
•
•
•
Age > 60 y.o.
Temp > 38.3 C
Albumin < 2.5 mg/dl
WBC > 15,000
Rx in ICU
Pseudomembranes
Points
1
1
1
1
2
2
Mild 0-1, Severe 2 or more.
CDI Outcomes: Clinical Cure
Metronidazole
Vancomycin
Mild CDI
90%
98%
Severe CDI
76%
97%
Recurrences
15%
14%