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18 th March 2007ID in Diabetes1 Common Infectious Diseases in Diabetic Patients Dr Wu Tak Chiu Division of Infectious Diseases Department of Medicine Queen.

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Presentation on theme: "18 th March 2007ID in Diabetes1 Common Infectious Diseases in Diabetic Patients Dr Wu Tak Chiu Division of Infectious Diseases Department of Medicine Queen."— Presentation transcript:

1 18 th March 2007ID in Diabetes1 Common Infectious Diseases in Diabetic Patients Dr Wu Tak Chiu Division of Infectious Diseases Department of Medicine Queen Elizabeth Hospital

2 18 th March 2007ID in Diabetes2 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

3 18 th March 2007ID in Diabetes3 DM and Infections  Many infections are more common in diabetic patients  Increased severity  Increased risk of complications

4 18 th March 2007ID in Diabetes4 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

5 18 th March 2007ID in Diabetes5 Observational studyPopulation Glucose cutoff mmol/l Risks Pomposelli et al 1998Post-op spot >12.2 on post-op Day 1 ↑2.7x nosocomial infection Latham et al 2001Cardiothoracic 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% Hyperglycaemia associated with Increased infection & Mortality

6 18 th March 2007ID in Diabetes6 Interventional StudyPopulations Target glucose level (mmol/l) OutcomesComments Furnary et al 1999 Post cardiothoracic surgery 8.3-11.1 24 hours post-op ↓deep sternal wound infection 0.8% vs 2.0% ↓cost and LOS lack of randomization used historical controls DIGAMI 1 Malmberg et al 1995 AMI 7.0-10.9; 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 2 Malmberg et al 2005 AMI7.0-10.0 No 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

7 18 th March 2007ID in Diabetes7 UTI Symptomatic UTI vs. Asymptomatic Bacteriuria (ASB)

8 18 th March 2007ID in Diabetes8 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%

9 18 th March 2007ID in Diabetes9

10 18 th March 2007ID in Diabetes10 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

11 18 th March 2007ID in Diabetes11 Distribution of bacterial isolates in urine from QEH AED from 2004 to May 2006

12 18 th March 2007ID in Diabetes12 Antimicrobial Therapy  Choice of antibiotics in UTI Trimethroprim-sulfamethoprim (TMP-SMZ) Fluroquinolones Nitrofurantoin Beta-lactam

13 18 th March 2007ID in Diabetes13 Antimicrobial Susceptibility Profile for Urine Specimens at QEH AED from 2004 to 2006 May

14 18 th March 2007ID in Diabetes14 E. coli Against Nitrofurantoin  100 E-coli isolates from urine culture at different wards at QEH were randomly chosen for testing sensitivity against Nitrofurantoin

15 18 th March 2007ID in Diabetes15 % of Antibiotics resistance among the most common isolates of UTI in GOPC E-coliKlebProteus Total no.1160153104

16 18 th March 2007ID in Diabetes16 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

17 18 th March 2007ID in Diabetes17  Concerns Wide spread of resistance > 30-40 % of E coli from community acquired UTI are resistant Cannot be used in pregnancy

18 18 th March 2007ID in Diabetes18 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

19 18 th March 2007ID in Diabetes19  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

20 18 th March 2007ID in Diabetes20 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

21 18 th March 2007ID in Diabetes21 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

22 18 th March 2007ID in Diabetes22 Beta-lactam  Choice: Amoxicillin/Clavulanate (Augmentin) Oral 2 nd generation cephalosporins (Zinnat)  Ampicillin generally is not a choice because most E-coli are resistant.

23 18 th March 2007ID in Diabetes23 Oral Augmentin vs. Zinnat Amoxil-clavulanate (oral) Cefuroxime-axetil Oral bioavailabilityGoodFair Microbiological susceptibility result More favorableLess favorable Genetic Resistance barrier HighLow PriceLowHigh

24 18 th March 2007ID in Diabetes24  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

25 18 th March 2007ID in Diabetes25 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

26 18 th March 2007ID in Diabetes26 Asymptomatic Bacteriuria (ASB) in Diabetic Women

27 18 th March 2007ID in Diabetes27 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?

28 18 th March 2007ID in Diabetes28 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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32 18 th March 2007ID in Diabetes32  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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38 18 th March 2007ID in Diabetes38 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

39 18 th March 2007ID in Diabetes39 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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41 18 th March 2007ID in Diabetes41 Diabetic Foot Infections

42 18 th March 2007ID in Diabetes42 DM Foot Infections  Risk Factors: Men DM >10yrs Poor glycaemic control CVS, retinal or renal complications

43 18 th March 2007ID in Diabetes43 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

44 18 th March 2007ID in Diabetes44

45 18 th March 2007ID in Diabetes45 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.

46 18 th March 2007ID in Diabetes46 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%

47 18 th March 2007ID in Diabetes47 Diagnostic Clues of Underlying Osteomyelitis  Clinical Findings: Ulcer area > 2cm ² ( 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

48 18 th March 2007ID in Diabetes48 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

49 18 th March 2007ID in Diabetes49 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

50 18 th March 2007ID in Diabetes50 

51 18 th March 2007ID in Diabetes51 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

52 18 th March 2007ID in Diabetes52 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/2 nd or 3 rd cephalosporin Vancomycin for MRSA

53 18 th March 2007ID in Diabetes53 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

54 18 th March 2007ID in Diabetes54 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

55 18 th March 2007ID in Diabetes55 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)

56 18 th March 2007ID in Diabetes56 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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59 18 th March 2007ID in Diabetes59 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

60 18 th March 2007ID in Diabetes60 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

61 18 th March 2007ID in Diabetes61 Thank You.

62 18 th March 2007ID in Diabetes62

63 18 th March 2007ID in Diabetes63 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

64 18 th March 2007ID in Diabetes64 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 1 st episode of uncomplicated UTI in young woman.

65 18 th March 2007ID in Diabetes65  Indication of screening of asymptomatic bacteriuria Pregnant women Patient undergoing urological examination Renal transplant patient

66 18 th March 2007ID in Diabetes66 Recurrent infection in young women  Common in women  20% developed 2 nd infection during FU period of 6 months  Management Continuous prophylaxis Post-coital prophylaxis Intermittent self-treatment

67 18 th March 2007ID in Diabetes67 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

68 18 th March 2007ID in Diabetes68 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

69 18 th March 2007ID in Diabetes69 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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