18 th march 2007id in diabetes1 common infectious diseases in diabetic patients dr wu tak chiu...

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


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


DM and Infections

Many infections are more common in diabetic patients

Increased severity Increased risk of complications


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


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


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


UTI

Symptomatic UTI

vs.

Asymptomatic Bacteriuria (ASB)


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%


UTI & Diabetics

Same pathogens as non-diabeticsE. coli is commonest pathogenKlebsiella pneumoniae, Gp B streptococci and

C. albicans are more common in diabetics


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


Antimicrobial Therapy

Choice of antibiotics in UTITrimethroprim-sulfamethoprim (TMP-SMZ)FluroquinolonesNitrofurantoinBeta-lactam


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


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%


% 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


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


ConcernsWide spread of resistance> 30-40 % of E coli from community acquired

UTI are resistantCannot be used in pregnancy


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


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


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


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


Beta-lactam

Choice:Amoxicillin/Clavulanate (Augmentin)Oral 2nd generation cephalosporins (Zinnat)

Ampicillin generally is not a choice because most E-coli are resistant.


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


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



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


Asymptomatic Bacteriuria (ASB) in Diabetic Women


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?


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


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


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


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


Diabetic Foot Infections


DM Foot Infections

Risk Factors:MenDM >10yrsPoor glycaemic control CVS, retinal or renal complications


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


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.


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%


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


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


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


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



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


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.


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


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)


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


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


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


Thank You.


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


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.


Indication of screening of asymptomatic bacteriuriaPregnant womenPatient undergoing urological examinationRenal transplant patient


Recurrent infection in young women

Common in women 20% developed 2nd infection during FU

period of 6 monthsManagement

Continuous prophylaxisPost-coital prophylaxisIntermittent self-treatment


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


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


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

18 th march 2007id in diabetes1 common infectious diseases in diabetic patients dr wu tak chiu...

Documents

nitrofurantoin slide

enterococcus slide

ptb slide

diabetes9 slide

pregnancy slide

wound infection rate

immune function slide

diabetes7 uti symptomatic