Common Infectious Diseases

in
Diabetic Patients
Dr Wu Tak Chiu
Division of Infectious Diseases
Department of Medicine
Queen Elizabeth Hospital

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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
Glucose cutoff
Observational study Population Risks
mmol/l

spot >12.2 on post-op

Pomposelli et al 1998 Post-op ↑2.7x nosocomial infection
Day 1

hyperglycemia in first
Latham et al 2001 Cardiothoracic post-op ↑2x surgical site infection
48 hrs

↑3x in-hospital or 30-day

ischemic stroke with no
Capes et al 2001 admission glucose >6.1 mortality and poor functional
hx of DM
outcome

Umpierrez GE et al newly diagnosed DM vs FBS>7.0 or ↑mortality

2002 known DM vs normal random>11.1 16% vs 3% vs 1.7%

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 Good Glycaemic Control
Decreased Wound Infection Rate

Target glucose level

Interventional Study Populations Outcomes Comments
(mmol/l)

↓deep sternal wound

infection 0.8% vs lack of randomization
Post cardiothoracic 8.3-11.1
Furnary et al 1999 2.0%
surgery 24 hours post-op
used historical controls
↓cost and LOS

7.0-10.9; ↓mortality 29% at 1 yr

DIGAMI 1 ? in-pt or both in-pt and out-pt
AMI mean glucose 9.6 vs 28% at 3.4 yrs
Malmberg et al 1995 glycemic control accountable
11.7 NNT=9

No sig diff in glucose levels

DIGAMI 2 No sig difference in
AMI 7.0-10.0 among three groups (end A1c
Malmberg et al 2005 mortality
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

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 Antimicrobial Therapy
 Choice of antibiotics in UTI
 Trimethroprim-sulfamethoprim (TMP-SMZ)
 Fluroquinolones
 Nitrofurantoin
 Beta-lactam

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 Antimicrobial Susceptibility Profile for Urine
Specimens at QEH AED from 2004 to 2006
May

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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

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 % of Antibiotics resistance among the
most common isolates of UTI in GOPC
E-coli Kleb Proteus
Total no. 1160 153 104

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Trimethroprim-sulfamethoprim (TMP-
SMZ)
 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 Cefuroxime-axetil
(oral)

Oral bioavailability Good Fair

Microbiological More favorable Less favorable

susceptibility result

Genetic Resistance High Low

barrier

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

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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%)

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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