Common Infectious Diseases in Diabetic Patients

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

2. Topics to be covered • Pathogenesisof 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 ID in Diabetes

3. DM and Infections • Many infections are more common in diabetic patients • Increased severity • Increased risk of complications 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 ID in Diabetes

5. Hyperglycaemia associated with Increased infection & Mortality ID in Diabetes

6. Good Glycaemic Control Decreased Wound Infection Rate ID in Diabetes

7. UTI Symptomatic UTI vs. Asymptomatic Bacteriuria (ASB) 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% 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 ID in Diabetes

11. Distribution of bacterial isolates in urine from QEH AED from 2004 to May 2006 ID in Diabetes

12. Antimicrobial Therapy • Choice of antibiotics in UTI • Trimethroprim-sulfamethoprim (TMP-SMZ) • Fluroquinolones • Nitrofurantoin • Beta-lactam ID in Diabetes

13. Antimicrobial Susceptibility Profile for Urine Specimens at QEH AED from 2004 to 2006 May 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 ID in Diabetes

15. % of Antibiotics resistance among the most common isolates of UTI in GOPC 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 ID in Diabetes

17. Concerns • Wide spread of resistance • > 30-40 % of E coli from community acquired UTI are resistant • Cannot be used in pregnancy 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 ID in Diabetes

19. 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 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 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 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. ID in Diabetes

23. Oral Augmentin vs. Zinnat 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 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 ID in Diabetes

26. Asymptomatic Bacteriuria (ASB) in Diabetic Women 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? ID in Diabetes

28. 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 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 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 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 ID in Diabetes

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41. Diabetic Foot Infections ID in Diabetes

42. DM Foot Infections • Risk Factors: • Men • DM >10yrs • Poor glycaemic control • CVS, retinal or renal complications 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 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. 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 rateover 1-3 years is 40% 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 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 10-20 days after infection • Other imaging studies not cost-effective 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 ID in Diabetes

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