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18th March 2007 ID in Diabetes 1
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 ManagementUTI: symptomatic and asymptomaticDM footChest 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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Observational study PopulationGlucose cutoff
mmol/lRisks
Pomposelli et al 1998 Post-opspot >12.2 on post-op
Day 1↑2.7x nosocomial infection
Latham et al 2001 Cardiothoracic post-ophyperglycemia in first
48 hrs↑2x surgical site infection
Capes et al 2001ischemic stroke with no
hx of DMadmission glucose >6.1
↑3x in-hospital or 30-day mortality and poor functional
outcome
Umpierrez GE et al 2002
newly diagnosed DM vs known DM vs
normal
FBS>7.0 or random>11.1
↑mortality16% vs 3% vs 1.7%
Hyperglycaemia associated with Increased infection & Mortality
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Interventional Study PopulationsTarget glucose level
(mmol/l)Outcomes Comments
Furnary et al 1999Post cardiothoracic
surgery8.3-11.1
24 hours post-op
↓deep sternal wound infection 0.8% vs
2.0%
↓cost and LOS
lack of randomization
used historical controls
DIGAMI 1Malmberg et al 1995
AMI7.0-10.9;
mean glucose 9.6 vs 11.7
↓mortality 29% at 1 yr 28% at 3.4 yrs
NNT=9
? in-pt or both in-pt and out-pt glycemic control accountable
DIGAMI 2Malmberg et al 2005
AMI 7.0-10.0No sig difference in
mortality
No sig diff in glucose levels among three groups (end A1c
6.8%) Underpowered study
Good Glycaemic Control Decreased Wound Infection Rate
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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 diabeticsGas 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-diabeticsE. coli is commonest pathogenKlebsiella 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
55%
7%
9%
8%
3%
1%
3%
10%
3% 1% 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 UTITrimethroprim-sulfamethoprim (TMP-SMZ)FluroquinolonesNitrofurantoinBeta-lactam
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Antimicrobial Susceptibility Profile for Urine Specimens at QEH AED from 2004 to 2006
May
Ampicillin
Augmentin
Cefuroxime
Ceftazidime #
Ceftriaxone
Cefotaxime #
Cefepime #
% ESBL
1
Ciprofloxacin
Levofloxacin
Unasyn
Co-trimoxazol
e
Imipenem
Meropenem
Gentamicin
Amikacin
Timentin
Tazocin
Sulperazon
Penicillin
Clindamycin
Fusidic Acid
Vancomyci
n
E. coli 67 7 19 See ESBL 15 34 30 30 43 0 0 28 1 5 1 1
Klebseilla 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
Morganella 100 92 73 4 0 3 0 11 16 37 54 0 0 27 0 5 0 0
Ps. aeruginosa 3 6 21 8 3 3 1 3 *
Enterococcus 4 4 0
Strep. Group B 0 0 0 37 0
Staph. aureusψ 0 5 0 0
MRSA 1 1 5 7 1 4 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
Sensitive94%
Resistant6%
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% of Antibiotics resistance among the most common isolates of UTI in GOPC
0%20%40%60%80%
100%
Ampicillin AugmentinNitrofuratoin
Cotrimoxazole
Ofloxacin
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 saprophyticusGroup B streptococcusNo activity on Pseudomonas aeruginosa, enterococcus
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ConcernsWide spread of resistance> 30-40 % of E coli from community acquired
UTI are resistantCannot 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, enterococciPseudomonas aeruginosa
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ConcernsWide spread of resistanceAbout 20-30 % of E. coli in community acquired
UTI are resistantInduce 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. faecalisKlebsiella spp. & Proteus are usually resistantNot 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 upsetPneumonitis, 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. ampicillinDifference is significant but not bigHigh resistance rate in HK for TMP/SMZ and quinolones
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Antimicrobial Therapy
Choice of antibiotics in UTITrimethroprim-sulfamethoprim (TMP-SMZ)FluroquinolonesNitrofurantoinBeta-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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MethodsDiabetic women >16 yrs of ageBacteriuria without urinary symptoms50 received placebo55 received 14 days antibioticsScreened 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 effectsAssociated 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 womanBefore urological interventionRenal transplant patient
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Diabetic Foot Infections
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DM Foot Infections
Risk Factors:MenDM >10yrsPoor 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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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 aTIFF (Uncompressed) decompressor
are needed to see this picture.
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Aggressive Surgical ApproachGibbons 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 InterventionTan 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 tuberculosisShaikh 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
urine75 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 infectionComplicated UTIRecurrent 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 bacteriuriaPregnant womenPatient undergoing urological examinationRenal transplant patient
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Recurrent infection in young women
Common in women 20% developed 2nd infection during FU
period of 6 monthsManagement
Continuous prophylaxisPost-coital prophylaxisIntermittent 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 prophylaxisOther methods:
Avoid use of diaphragm /spermicidePost-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