Document 11580

“arguably the greatest risk … to human
health comes in the form of
antibiotic-resistant bacteria. We live
in a bacterial world where we will
never be able to stay ahead of the
mutation curve. A test of our
resilience is how far behind the curve
we allow ourselves to fail.”
World Economic Forum, 2013
First, do no harm
HIV

Review of 162 HIV pts hospitalized at
Cleveland Clinic in 2011
 50% errors in prescriptions for ARV
 65% of these errors not corrected by discharge
▪ E.Neuner. Abstract #36170, ID Week, San Diego 2012
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Postulated reasons
 Complexity of regimens
 Unfamiliarity re HIV Rx by hospital MD’s
▪ Shift of therapy to outpatient setting
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ART should be offered regardless of CD4
count
ART is recommended to persons during acute
phase of primary HIV infection regardless of
symptoms
ART should be started as soon as possible in
pts with opportunistic infections
 TB and Cryptococcus can be exceptions
* JAMA. 2012; 308(4): 387-402

ART should be offered regardless of CD4
count
 There is a steady decrease in AIDS-free survival as
CD4 threshold for initiation of Rx decreased.
 The higher the CD4 achieved after ART, the
greater the survival benefit
 ART reduces likelihood of HIV transmission
▪ Cohen MS, et al. N Engl J Med 2011;365:493-505

ART is recommended to persons during acute
phase of primary HIV infection regardless of
symptoms. Early Rx associated with:
 Conserved lymphocyte function
 Lowered cell-associated HIV DNA
 Reduction in viral set point
 Delayed rate of CD4 cell decline
 Theoretical decline in transmission because of
high viral load in newly infected individuals
Pneumocystis

ART should be started as soon as possible in
pts with opportunistic infections
 Usually start within 2 weeks of diagnosis
 Cryptococcal meningitis is less certain because of
association of increased mortality with early Rx
 In TB, may delay ART Rx when CD4 > 50 to avoid
immune reconstitution syndrome

What to start
 Prior to Rx should check genotype susceptibility
 Always treat with multiple agents (usually
minimum of 3)
 Convenience of regimen is important as compliance
is key to good outcome
 Specialist involvement improves patient outcomes
The desire to take medicine is perhaps the
greatest factor which distinguishes man from
animals.
Sir William Osler

Indications for screening for ASB in adults
includes:
 Pregnancy
 Prior to urologic procedures where mucosal
bleeding is anticipated.
No other adults with ASB should be treated
CID. 2005;40:643-54

Screening for or treatment of ASB is not
recommended for the following:
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Presence of pyuria
Nonpregnant women
Diabetic women
Elderly persons, whether or not institutionalized
Spinal cord injuries
Catheterized patients
Renal or other solid organ transplant

The Role of Asymptomatic Bacteruria in
Young Women With Recurrent Urinary Tract
Infections: To Treat or Not to Treat?

673 young women with ASB
 312 not treated, 361 treated
 13.1% not treated had recurrence at 12 mos
 46.8% treated group had recurrence at 12 mos
Cai T. Clin Infect Dis. 2012;55:771-777
Table 2. Prevalence of asymptomatic bacteriuria in selected populations.
Population
Healthy, premenopausal women
Pregnant women
Postmenopausal women aged 50–70 years
Diabetic patients
Women
Men
Elderly persons in the community
Women
Men
Elderly persons in a long-term care facility
Women
Men
Patients with spinal cord injuries
Intermittent catheter use
Sphincterotomy and condom catheter in place
Patients undergoing hemodialysis
Patients with indwelling catheter use
Short-term
Long-term
Prevalence, %
1.0–5.0
1.9–9.5
2.8–8.6
9.0–27
0.7–11
10.8–16
3.6–19
25–50
15–40
23–89
57
28
9–23
100
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Patients in nursing homes are frequently
evaluated for lethargy/stupor
These patients frequently have ASB
In the absence of fever and/or leukocytosis,
the depressed mental status is seldom due to
UTI. (Dr. Pontzer’s observations – unpublished)
Many other factors, including dehydration,
medications and metabolic factors are common
causes

The downside for treatment of ASB include:
 C. diff
 C. diff
 C. diff
 Colonization/infection with multidrug-resistant
bacteria in both the index patient and those
patients surrounding him/her.
 Other adverse drug reactions

If your patient is afebrile and
hemodynamically stable, recommend in
most cases refrain from antibiotic treatment
for ASB
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246 pts with CDI reviewed
141 received non-CDI ABX Rx during and/or
shortly after their CDI Rx totaling 445 courses
77% received at least 1 unnecessary ABX dose
26% of ABX Rx was totally unnecessary
Leading indications for unnecessary Rx
were putative UTI or pneumonia
Shaughnessy MK, et al. Infect Control Hosp Epidemiol 2013;34:109-116
HIGH RISK
MEDIUM RISK LOW or NO
RISK
Cephalosporins ß-lactam
Sulfonamides
3rd & 4th gen
Narrow
Tigecycline
spectrum
Quinolones
Carbapenems
Vancomycin
Clindamycin
TMP/SMX
Broad Spectrum Tetracyclines
Penicillins
Macrolides
Metronidazole
Linezolid &
Daptomycin
Nitrofurantoin

Discontinue the inciting antibiotic therapy

Mild disease → po metronidazole 500 mg tid or
vanco 125 mg qid for 10-14 days

Moderately severe disease → po vancomycin with
or without IV metronidazole
Cohen SH, et al. Infect Control Hospit Epidiemol. 2010; 31: 421-55

Fulminant disease → po vanco (500 mg qid) &/or
intraluminal vanco (500 mg 3-4 x day) with IV
metronidazole (500 mg q 8h)
 Criteria for subtotal colectomy: age >65 with a
WBC
>50,000 and/or lactate > 5 mmol/L
 Right-sided colonic lavage as substitute for subtotal
colectomy may be viable option*
 IVIG reported effective in some case reports
▪ Controlled studies remain to be done
*Lamontagne et al. Ann Surg. 2007;245:267

Fidaxomicin
 Narrower spectrum than vanco or metronidazole
▪ Less disruption of colonic flora
 Lower recurrence (10% v 28%) with non NAP1
strains
▪ No difference with NAP1 strains
 Expensive ~$3000 per course
Louie et al. N Engl J Med. 2011;364:422
“No antimicrobial agent is clearly superior for
the initial cure of C. difficile infection”
Dimitri, DM. et al. Ann Intern Med 2011;155:839-847

My current favorite po vancomycin pulse
taper regimen:
 Week 1: 125 mg po qid
 Week 2: 125 mg po bid
 Week 3: 125 mg po daily
 Week 4-7: 125 mg po every other day
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Fecal transplant following 4 days po vanco vs. po
vancomycin 500 mg po qid X 14 days
81% cure with transplant
 2 of 3 who failed were cured with 2nd transplant
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27% cure with standard vanco Rx
Donor screening included risk factor
questionnaire, parasites, C. diff, pathogenic
bacteria, HIV, hepatitis A,B,C, CMV, EBV, Syphilis,
serologies for Strongyloides & Amoeba
Nood, E. et al. N Engl J Med 2013;368:407-15
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Synthetic stool – RePOOPulate
 Mixture of 33 different intestinal bacteria isolated
in pure culture
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Treated 2 patients who had failed at least 3
courses of Rx for hypervirulent CDI
 Both were asymptomatic at 6 month follow-up
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Eliminates concern for disease transmission
Eliminates ‘yuk’ factor
Petrof, E O, et al. Microbiome 2013; 1: 3
S. aureus
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20-40 % mortality
Leading cause of both community and
hospital acquired bacteremia
Complications include endocarditis,
osteomyelitis, discitis, joint infection ,
endopthalmitis and many others
Recurrence of bacteremia is common
Sexton, D. et al. Treatment of Staphylococcus aureus bacteremia in adults
UpToDate Jan 2013
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Endocarditis frequency 25-32%
TEE often indicated since presence of
vegetation can impact management
 Occasional exceptions may include rapid
clearance of bacteremia in the presence of a
removable focus (i.e. vascular catheter)
 TTE is inadequate for ruling out IE
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Vancomycin
 Dose must be adjusted based upon patient mass
and creatinine clearance
 Follow trough vanco levels
▪ For sepsis target 15-20 ug/ml
▪ Should be obtained at steady state
 Consider shift to another agent if MIC is > 2 ug/ml
 Change to beta-lactam if organism is MSSA
▪ Superiority supported by multiple studies

Daptomycin (Cubicin®)
 Effective against most MRSA & MSSA
 Not indicated for pneumonia
 Monitor CPK weekly
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Linezolid (Zyvox®)
 Effective against most MSSA & MRSA
 Lack of cidality suboptimal for endocarditis
 Not FDA approved for SAB
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Ceftaroline (Teflaro®)
 5th generation cephalosporin
 Active against MRSA
 It is bactericidal
 Not FDA approved for bacteremia/sepsis
▪ Only for SSI (MRSA and MSSA) and community acquired
pneumonia (not MRSA)
 Overuse may well lead to resistance
 Q 12 hr dose may be suboptimal for sepsis
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Removable focus
 Retaining an IV foreign body greatly reduces
probability for cure – ideally remove infected
devices
 Presence of cardiac devices decrease cure rate
▪ Chamis AL, et al. Circulation 2001; 104:1029

Patients who have a removable focus may be
treated with a 14 day course of IV ABX Rx if all
of the following are present:
 Blood cultures clear within 4 days of onset Rx
 No valvular abnormalities
 No indwelling devices: prosthetic joints, heart
valves or vascular grafts
 No evidence for metastatic infection
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All others should receive 4-6 wks IV ABX Rx
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Multiple studies conclude that patients with
SAB have improved outcomes with an ID
consult
 Forsblom E, et al. CID 2013;56:527
 Jenkins TC, et al. CID 2008; 46:1000
 Honda H, et al. Am J Med 2010;123:631
 Lahey T, et al. Medicine 2009; 88: 263
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