Download Infections In Diabetic Patients

Common Infectious Diseases
in
Diabetic Patients
Dr Wu Tak Chiu
Division of Infectious Diseases
Department of Medicine
Queen Elizabeth Hospital
18th March 2007
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Topics to be covered
 Pathogenesis of increased risk of infection
in DM patients
 DM associated infection disease + Clinical
Management
 UTI: symptomatic and asymptomatic
 DM foot
 Chest infection: Influenza A, Pneumococcus,
PTB
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DM and Infections
 Many infections are more common in
diabetic patients
 Increased severity
 Increased risk of complications
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Suppressed Immunity in DM Patients
 PMN functions  (particular when acidosis is
present):
 Lecukocyte adherence 
 Chemotaxis 
 Phagocytosis 
 Antioxidant activities 
 But response to vaccines appear to be normal
 Improving glycemic control might improve immune
function
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Hyperglycaemia associated with
Increased infection & Mortality
Observational study
Population
Glucose cutoff
mmol/l
Risks
Pomposelli et al 1998
Post-op
spot >12.2 on post-op
Day 1
↑2.7x nosocomial infection
Latham et al 2001
Cardiothoracic post-op
hyperglycemia in first
48 hrs
↑2x surgical site infection
Capes et al 2001
ischemic stroke with no
admission glucose >6.1
hx of DM
Umpierrez GE et al
2002
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newly diagnosed DM vs
known DM vs normal
FBS>7.0 or
random>11.1
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↑3x in-hospital or 30-day
mortality and poor functional
outcome
↑mortality
16% vs 3% vs 1.7%
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Good Glycaemic Control
Decreased Wound Infection Rate
Interventional Study
Furnary et al 1999
Populations
Post cardiothoracic
surgery
Target glucose level
(mmol/l)
8.3-11.1
24 hours post-op
Outcomes
Comments
↓deep sternal wound
infection 0.8% vs
2.0%
lack of randomization
used historical controls
↓cost and LOS
DIGAMI 1
Malmberg et al 1995
DIGAMI 2
Malmberg et al 2005
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AMI
AMI
7.0-10.9;
↓mortality 29% at 1 yr
mean glucose 9.6 vs
28% at 3.4 yrs
11.7
NNT=9
7.0-10.0
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No sig difference in
mortality
? in-pt or both in-pt and out-pt
glycemic control accountable
No sig diff in glucose levels
among three groups (end A1c
6.8%)
Underpowered study
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UTI
Symptomatic UTI
vs.
Asymptomatic Bacteriuria (ASB)
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Symptomatic UTI and Diabetes
 The clinical features, diagnosis and treatment of
uncomplicated UTIs in diabetics are the same as
for non-diabetics
 Rare emphysematous UTI
 Pyelonephritis, pyelitis and cystitis
 > 90% occur in diabetics
 Gas formation
 Seen in plan X-ray or CT
 Antibiotics + open drainage +/- nephrectomy
 Overall mortality rate was 18.8%
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UTI & Diabetics
 Same pathogens as non-diabetics
 E. coli is commonest pathogen
 Klebsiella pneumoniae, Gp B streptococci and
C. albicans are more common in diabetics
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Distribution of bacterial isolates in urine
from QEH AED from 2004 to May 2006
3% 1%
10%
3%
1%
3%
8%
55%
9%
7%
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E coli
Klebseilla
Coliforms
Proteus miribalis
Group B Strep
S saprophyticus
S aureus
Enterococcus
P aureginosa
Acinetobacter spp
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Antimicrobial Therapy
 Choice of antibiotics in UTI
 Trimethroprim-sulfamethoprim (TMP-SMZ)
 Fluroquinolones
 Nitrofurantoin
 Beta-lactam
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Co-trimoxazol
e
Imipenem
Meropenem
Gentamicin
Amikacin
Timentin
Tazocin
Sulperazon
30
43
0
0
28
1
5
1
1
100
20
14
See ESBL
9
17
18
33
26
0
0
6
0
14
4
1
Proteus miribalis
71
17
20
17
7
19
20
20
31
41
33
0
0
11
1
2
0
0
Coliforms
86
61
39
21
7
18
2
24
14
48
32
0
0
22
1
18
4
11
100
92
73
4
0
3
0
11
16
37
54
0
0
27
0
5
0
0
6
21
8
3
3
1
3
*
Klebseilla
Morganella
Ps. aeruginosa
Enterococcus
3
4
Strep. Group B
4
0
0

Staph. aureus
MRSA
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Vancomycin
Unasyn
30
Fusidic Acid
Levofloxacin
34
Clindamycin
Ciprofloxacin
15
Penicillin
% ESBL1
See ESBL
Cefepime #
19
Cefotaxime #
Cefuroxime
7
Ceftriaxone
Augmentin
67
E. coli
Ceftazidime #
Ampicillin
Antimicrobial Susceptibility Profile for Urine
Specimens at QEH AED from 2004 to 2006
May
0
37
0
0
5
0
0
11
57
14
0
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E. coli Against Nitrofurantoin
 100 E-coli isolates from urine culture at different wards at
QEH were randomly chosen for testing sensitivity against
Nitrofurantoin
R e si st a nt
6%
S e nsi t i ve
94%
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% of Antibiotics resistance among the
most common isolates of UTI in GOPC
Total no.
E-coli
1160
Kleb
153
Proteus
104
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Ofloxacin
Cotrimoxazole
Nitrofuratoin
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Augmentin
Ampicillin
100%
80%
60%
40%
20%
0%
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Trimethroprim-sulfamethoprim (TMPSMZ)
 Well absorbed orally
 Excreted primarily in urine
 Use as standard for comparison of efficacy in
treatment of UTI
 Sufficient data to support 3 days treatment in
uncomplicated cystitis
 Spectrum of activity




Enterobacteriaceae (E coli, Klebseilla, Proteus)
Staphylococcus aureus, S saprophyticus
Group B streptococcus
No activity on Pseudomonas aeruginosa, enterococcus
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 Concerns
 Wide spread of resistance
 > 30-40 % of E coli from community acquired
UTI are resistant
 Cannot be used in pregnancy
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Fluoroquinolones
 Excellent bioavailability ( ORAL =IV)
 Good tissue penetration including kidney, prostate,
genital tract
 Long serum half life
 Sufficient data to support 3 days treatment for
uncomplicated UTI
 Spectrum of activity
 Enterobacteriaceae ( E coli, Klebseilla, Proteus)
 Some activity against S. aureus, S saprophyticus and
Streptococcus, enterococci
 Pseudomonas aeruginosa
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 Concerns
 Wide spread of resistance
 About 20-30 % of E. coli in community acquired
UTI are resistant
 Induce multiple drug resistance such as ESBL E.
coli
 Cannot be used in children and pregnant
woman
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Nitrofurantoin




Urinary antiseptics
Cannot achieve therapeutic level in blood
Low incidence of resistance even with 4 decades of use
Spectrum of activity
 E coli, (even some ESBL+ve strains in vitro)
 Some activity against gram +ve org such as S.
saprophyticus and E. faecalis
 Klebsiella spp. & Proteus are usually resistant
 Not active against Pseudomonas species
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Nitrofurantoin
 Concerns
 Mostly for treatment of lower UTI.
 Should not be used in patients with systemic sepsis
because of low serum level.
 Contraindicated in patients with impaired renal
function because decrease concentration in urine and
increase serum level causing toxicity
 Special caution for elderly because of renal
impairment and high incidence of serious side effect
 Side effects:
 GI upset
 Pneumonitis, polyneuropathy, hepatitis, bone marrow
suppression
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Beta-lactam
 Choice:
 Amoxicillin/Clavulanate (Augmentin)
 Oral 2nd generation cephalosporins (Zinnat)
 Ampicillin generally is not a choice because
most E-coli are resistant.
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Oral Augmentin vs. Zinnat
Amoxil-clavulanate
(oral)
Cefuroxime-axetil
Oral bioavailability
Good
Fair
Microbiological
susceptibility result
More favorable
Less favorable
Genetic Resistance
barrier
High
Low
Price
Low
High
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 Most reviews consider that Beta-lactam in general
is inferior than TMP/SMZ and quinolones in
eradication of bacteriuria or may associate with
higher rate of recurrence
 However,
 Conclusion drawn from studies using different kind of
beta-lactam, e.g. ampicillin
 Difference is significant but not big
 High resistance rate in HK for TMP/SMZ and quinolones
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Antimicrobial Therapy
 Choice of antibiotics in UTI
 Trimethroprim-sulfamethoprim (TMP-SMZ)
 Fluroquinolones
 Nitrofurantoin
 Beta-lactam
 Therefore, nitrofurantoin (Lower UTI) or
Amoxicillin/Clavulanate is a good choice for
empirical treatment for community acquired UTI in
Hong Kong
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Asymptomatic Bacteriuria (ASB) in
Diabetic Women
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Asymptomatic Bacteriuria (ASB) in Diabetics
 Questions:
 Should we screen for asymptomatic bacteriuria in
diabetics?
 Should we treat ASB in diabetics?
 Do the diabetic women :
 have higher incidence rate of ASB?
 with ASB have higher risk of developing symptomatic UTI
than those without ASB?
 with ASB have poor long term prognosis than those without
ASB?
 with ASB have higher risk of developing long term
complications such deterioration of RFT?
 with ASB benefit from antibiotic therapy by reducing the risk
of developing symptomatic UTI?
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ASB in Diabetes
 Definition:
 Presence of high quantities of a uropathogen in the urine of an
asymptomatic person
 Colony count ≥ 10^5cfu.ml x 2 times
 3-4 times increase in risk of bacteriuria in diabetic women (26% vs.
6%)
 Risk factors:
 Longer diabetes duration (>10yrs, relative risk 2.6)
 Macroabluminuria
 Non-circumcised partners?
 But no association with current HBA1c level or glucose control
 Microbiology:
 E. coli and other gram-negative organisms
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 Methods
 Diabetic women >16 yrs of age
 Bacteriuria without urinary symptoms
 50 received placebo
 55 received 14 days antibiotics
 Screened for bacteriuria every 3 months for up
to 3 years
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Summary of
ASB in Diabetics
 ASB is more common in diabetic women but not men
 More likely to develop symptomatic UTI in asymptomatic
bacteriuric patient
 Does not have increased risk of faster decline in long term renal
function
 Antibiotic use:
 Not affect the frequency of or time to symptomatic infection,
including pyelonephritis,
 Recurrent asymptomatic bacteriuria in treating group is
common
 Antibiotic related adverse effects
 Associated with resistance development
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Recommendations for ASB in Diabetic Women
 NOT recommended for routine screening for
ASB in diabetics
 NOT recommended antibiotic therapy for
diabetic women who have ASB
 Except:
 Pregnant woman
 Before urological intervention
 Renal transplant patient
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Diabetic Foot Infections
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DM Foot Infections
 Risk Factors:
 Men
 DM >10yrs
 Poor glycaemic control
 CVS, retinal or renal complications
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Pathogenesis
 Neuropathy
 Sensory neuropathy   awareness of injury to the foot
 Motor neuropathy  intrinsic muscles of the foot  foot deformity
 maldistribution of weight
 Autonomous neuropathy   sweating  dry and cracked skin 
breaches in integrity of skin  entry of microorganism
 Superficial Fungal skin infection
 Higher rate of nasal and skin colonization with Staph. aureus
 Vasculopathy and Defects in immunity
  impair wound healing
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Diagnosis
 Difficult to differentiate
 infectious vs. non-infectious osteopathy;
 soft tissue infections alone vs. soft tissue
infections with osteomyelitis.
 Most patients with diabetic foot infection are
afebrile and have absence of local
inflammatory sign.
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Osteomyelitis in DM Foot
 1/3 of the diabetic patients with foot infection
are found to have evidence of osteomyelitis
 In patients with osteomyelitis, the cumulative
amputation rate over 1-3 years is 40%
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Diagnostic Clues of Underlying Osteomyelitis
 Clinical Findings:
 Ulcer area > 2cm² ( with sensitive of 56% & specificity of 92% )
 Deeper ulcers > 3mm (82% vs 33%)
 All exposed bone has underlying osteomyelitis
 Probe-to-bone test:
 positive predictive value of 89%
 Negative predictive value of 56%
 Some patients’ condition may appear less serious or more
superficial at presentation than they are found at surgical
exploration
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Diagnostic Clues of Underlying Osteomyelitis
 ESR:
 ESR of > 40mm/h associated with a 12-fold increased likelihood of
osteomyelitis in a prospective study (Diabetes 1991)
 X Ray:
 Bony abnormalities related to osteomyelitis are generally not
evident on plain films until 10-20 days after infection
 Other imaging studies not cost-effective
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Microbiology
 Simply swabbing the overlying ulcer often
yields organism that are colonizer and not
actually the causative agents
 Specimens from the deep tissue or bone
increase the likelihood of isolating true
pathogens
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
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Microbiology
 Deep diabetic foot infection is a classical
polymicrobial infection and anaerobic infection
 The conditions with the chronic ischemic tissue:
 favor the growth of obligate anaerobic bacteria
 Permitting synergic interactions with facultative bacteria
 Augment the overall microbial virulence of the infectious
process
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Antimicrobial Therapy
 Should receive therapy effective against S. aureus
and other aerobic gram-positive cocci.
 Expanding therapy to cover aerobic gram-negative
bacilli, anaerobic organism in patients with deep
infection
 For examples:







Ampicillin-clavulanic acid (Augmentin)
Ticaricillin-clavulanic acid (Timentin)
Cefoperazone-sulbactam (Sulperazon)
Piperacillin-tazobactam (Tazocin)
Carbapenem
Clindamycin + fluoroquinolone/2nd or 3rd cephalosporin
Vancomycin for MRSA
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Surgery
 If the infected bone can be easily resected without
compromising the integrity of the foot, this is
preferable to prolonged antibiotic therapy
 When the infection involves a digit, especially
other than the great toe, amputation may the most
cost-effective approach
QuickTime™ and a
TIFF (U ncompressed) decompressor
are needed to see this picture.
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Aggressive Surgical Approach
Gibbons Curr Clin Top Infect Dis 1994
 110 patients with histopathologically confirmed pedal
osteomyelitis
 76 of 86 patients (88%) with infection involving the
phalanges or metatarsal heads were cured by a combined
limited surgery (i.e., resection of a toe or ray or a
transmetatarsal amputation) and antibiotic therapy
 Left a weight-bearing surface in all patients
 Allowed antibiotic therapy to be limited to an average of
only ~2 weeks
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Early Surgical Intervention
Tan JS CID 1996
 Patients who had early local limited surgical intervention vs.
those who did not had a significantly lower rate of
subsequent above-ankle amputation (13% vs. 28%) and a
shorter duration of hospitalization (9.6 days vs. 18.8 days)
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Six Principles of Prevention of Foot Ulcers
1. Podiatric care
2. Pulse examination
3. Protective shoes
4. Pressure reduction
5. Prophylactic surgery
6. Patient Education
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Respiratory Tract Infections
 DM is not a significant independent risk factor for
death in elderly with pneumonia
 BUT:
  frequency with infections caused by S. aureus, GNB
and PTB
  Bacteremia and mortality in patients with
pneumonococcal pneumonia
  mortality and incidence of bacterial pneumonia during
epidemics of influenza
 Influenza and pneumococcal vaccines should be
considered for diabetics
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PTB and DM
 PTB DM patients had increased frequency
of lung lesions confined to lower lung
compared with PTB but w/o DM (23.5% vs.
2.4%)
 PTB DM patients had significant frequency
of cavitary lung lesions compared with PTB
but w/o DM (50.8% vs. 39%)
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Does diabetes alter the radiological presentation of pulmonary tuberculosis
Shaikh MA, et al Saudi Med J 2003
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Thank You.
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Dipstick leukocyte esterase test
 Rapid bedside screening test to detect pyuria
 Sensitive and specific in detecting > 10 WBC per mm3 of
urine
 75 to 96 % sensitivity
 94 to 98 % specificity
 Better when combine with nitrate ( positive only in nitrate
reducing bacteria e.g. E-coli, not in Staphylococcus
saprophyticus/enetercocci)
 Still have to take urine for microscopy if dipstick negative
but patient symptomatic
 Microscopic haematuria in acute dysuric woman is a
marker for acute cystitis because it is uncommon in
vaginitis or urethritis
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Urine culture
 Urine culture is advisable in symptomatic UTI if
 Suspected upper urinary tract infection
 Complicated UTI
 Recurrent UTI ( except those that are clearly
associated sexual activity)
 UTI in children<5
Urine culture is generally not needed for 1st
episode of uncomplicated UTI in young
woman.
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 Indication of screening of asymptomatic
bacteriuria
 Pregnant women
 Patient undergoing urological examination
 Renal transplant patient
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Recurrent infection in young women
 Common in women
 20% developed 2nd infection during FU
period of 6 months
 Management
 Continuous prophylaxis
 Post-coital prophylaxis
 Intermittent self-treatment
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Continuous prophylaxis
 Indication:
 2 or more symptomatic infections during 6 months
 3 or more symptomatic infections during 12 months
 Agents:
 Nitrofurantoin 50 /100 mg every night
 TMP/SMZ half a tablet every night
 Trimethoprim 100 mg every night
the last 2 agents cannot be used in pregnant women!
Trial basis for 6 months
 Can be used safely and effectively up to 2 -5 years without emergence
of resistance

 Start prophylaxis until urine culture is negative
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Post-coital regimen
 For those who describe a clear relation
between sexual intercourse and subsequent
cystitis
 Same dosage as the long term prophylaxis
 Other methods:
 Avoid use of diaphragm /spermicide
 Post-coital voiding is not shown to be useful
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Intermittent self treatment
 To begin a 3 days course of antibiotics agent
at the onset of symptoms
 Use standard dose in UTI
 Instruct patient to seek medical attention if
symptoms do not resolve within 48 to 72 hrs
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