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Common Infectious Diseases in Diabetic Patients

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Presentation on theme: "Common Infectious Diseases in Diabetic Patients"— Presentation transcript:

1 Common Infectious Diseases in Diabetic Patients
Dr Wu Tak Chiu Division of Infectious Diseases Department of Medicine Queen Elizabeth Hospital 18th March 2007 ID in Diabetes

2 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 18th March 2007 ID in Diabetes

3 DM and Infections Many infections are more common in diabetic patients
Increased severity Increased risk of complications 18th March 2007 ID in Diabetes

4 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 18th March 2007 ID in Diabetes

5 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 hx of DM admission 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 ↑mortality 16% vs 3% vs 1.7% 18th March 2007 ID in Diabetes

6 Good Glycaemic Control Decreased Wound Infection Rate
Interventional Study Populations Target glucose level (mmol/l) Outcomes Comments Furnary et al 1999 Post cardiothoracic surgery 24 hours post-op ↓deep sternal wound infection 0.8% vs 2.0% ↓cost and LOS lack of randomization used historical controls DIGAMI 1 Malmberg et al 1995 AMI ; 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 2 Malmberg et al 2005 No sig difference in mortality No sig diff in glucose levels among three groups (end A1c 6.8%) Underpowered study 18th March 2007 ID in Diabetes

7 Symptomatic UTI vs. Asymptomatic Bacteriuria (ASB)
18th March 2007 ID in Diabetes

8 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% 18th March 2007 ID in Diabetes

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10 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 18th March 2007 ID in Diabetes

11 Distribution of bacterial isolates in urine from QEH AED from 2004 to May 2006
18th March 2007 ID in Diabetes

12 Antimicrobial Therapy
Choice of antibiotics in UTI Trimethroprim-sulfamethoprim (TMP-SMZ) Fluroquinolones Nitrofurantoin Beta-lactam 18th March 2007 ID in Diabetes

13 Antimicrobial Susceptibility Profile for Urine Specimens at QEH AED from 2004 to 2006 May
18th March 2007 ID in Diabetes

14 E. coli Against Nitrofurantoin
100 E-coli isolates from urine culture at different wards at QEH were randomly chosen for testing sensitivity against Nitrofurantoin 18th March 2007 ID in Diabetes

15 % of Antibiotics resistance among the most common isolates of UTI in GOPC
E-coli Kleb Proteus Total no. 1160 153 104 18th March 2007 ID in Diabetes

16 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 18th March 2007 ID in Diabetes

17 Concerns Wide spread of resistance
> % of E coli from community acquired UTI are resistant Cannot be used in pregnancy 18th March 2007 ID in Diabetes

18 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 18th March 2007 ID in Diabetes

19 Concerns Wide spread of resistance
About % 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 18th March 2007 ID in Diabetes

20 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 18th March 2007 ID in Diabetes

21 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 18th March 2007 ID in Diabetes

22 Beta-lactam Choice: Amoxicillin/Clavulanate (Augmentin) Oral 2nd generation cephalosporins (Zinnat) Ampicillin generally is not a choice because most E-coli are resistant. 18th March 2007 ID in Diabetes

23 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 18th March 2007 ID in Diabetes

24 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 18th March 2007 ID in Diabetes

25 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 18th March 2007 ID in Diabetes

26 Asymptomatic Bacteriuria (ASB) in Diabetic Women
18th March 2007 ID in Diabetes

27 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? 18th March 2007 ID in Diabetes

28 ASB in Diabetes Definition: Risk factors: Microbiology:
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 18th March 2007 ID in Diabetes

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32 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 18th March 2007 ID in Diabetes

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38 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 18th March 2007 ID in Diabetes

39 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 18th March 2007 ID in Diabetes

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41 Diabetic Foot Infections
18th March 2007 ID in Diabetes

42 DM Foot Infections Risk Factors: Men DM >10yrs
Poor glycaemic control CVS, retinal or renal complications 18th March 2007 ID in Diabetes

43 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 18th March 2007 ID in Diabetes

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45 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. 18th March 2007 ID in Diabetes

46 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% 18th March 2007 ID in Diabetes

47 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 18th March 2007 ID in Diabetes

48 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 days after infection Other imaging studies not cost-effective 18th March 2007 ID in Diabetes

49 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 18th March 2007 ID in Diabetes

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51 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 18th March 2007 ID in Diabetes

52 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 18th March 2007 ID in Diabetes

53 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 18th March 2007 ID in Diabetes

54 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 18th March 2007 ID in Diabetes

55 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 days) 18th March 2007 ID in Diabetes

56 Six Principles of Prevention of Foot Ulcers
Podiatric care Pulse examination Protective shoes Pressure reduction Prophylactic surgery Patient Education 18th March 2007 ID in Diabetes

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59 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 18th March 2007 ID in Diabetes

60 Shaikh MA, et al Saudi Med J 2003
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 18th March 2007 ID in Diabetes

61 Thank You. 18th March 2007 ID in Diabetes

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63 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 18th March 2007 ID in Diabetes

64 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. 18th March 2007 ID in Diabetes

65 Indication of screening of asymptomatic bacteriuria
Pregnant women Patient undergoing urological examination Renal transplant patient 18th March 2007 ID in Diabetes

66 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 18th March 2007 ID in Diabetes

67 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 18th March 2007 ID in Diabetes

68 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 18th March 2007 ID in Diabetes

69 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 18th March 2007 ID in Diabetes


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