Complicated / Nosocomial UTI and Urosepsis What Can We Improve?

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1 Complicated / Nosocomial UTI and Urosepsis What Can We Improve? Kurt G. Naber Technical University of Munich, Germany Hangzhou, China, 13 September 2008

2 Complicated/Nosocomial UTI Causes: complicating factors (e.g. obstruction, stone) urologic interventions catheters or splints Localisations: lower urinary tract upper urinary tract Complications: change of pathogen development of resistance biofilm infection urosepsis

3 Contributing causes: International Herald Tribune, Monday, April 4, Parkinson s disease for over a decade; Pope John Paul II died on Saturday, April 2, 2005, from septic shock (urosepsis) and irreversible cardio-circulatory collapse... because of an overwhelming infection - episodes of respiratory insufficiency and constriction of the trachea; signs of heart damage; - and enlarged prostate gland, which made him vulnerable to the kind of urinary tract infection that killed him - He had been admitted twice to the Gemelli hospital clinic since Feb 1, the start of a slow two-month decline toward his death. Urosepsis due to catheter associated UTI

4 NIDEP 1 One Day Prevalence Study Nosocomial Infections 50% 40% UTI 30% 20% 10% 0% Pneumonia Wound Infec... Primary Sepsis Gastmeier P et al.: J Hosp Infect 1998; 38:37-49

5 Prevalence Study of NAUTI in Urological Departments (since 2003) Internet based Study ( sponsored by European Association of Urology (EAU) in cooperation with International Society of Chemotherapy (ISC) European Society of Clinical Microbiology and Infectious Diseases Federation of European Societies of Chemotherapy and Infection Interregional Association of Clinical Microbiology and Antimicrobial Chemotherapy (IACMAC) Asian Association of UTI and STD (AAUS) (since 2004) Confederacion Americana de Urologia (CAU) (since 2005)

6 PEP/PEAP Study (2003/04): Asia: Afghanistan 6 China 1 India 2 Iran 19 Iraq 2 Israel 2 Japan 7 Kazakhstan 1 Korea 5 Lebanon 1 Oman 1 Pakistan 9 S. Arabia 6 Singapore 1 Uzbekistan 2 Yemen 1 Europe: Albania 2 Armenia 1 Austria 10 Belarus 1 Belgium 6 Bosn.Herzeg 4 Bulgaria 5 Check Republ. 2 Croatia 4 Denmark 3 Estonia 4 France 4 Georgia 5 Germany 70 Gibraltar 1 Greece 9 Hungary 58 Italy 10 Latvia 3 Lithuania 1 Moldavia 1 Netherlands 5 Norway 7 Poland 4 Portugal 2 Romania 5 Russia 20 Serbia and M. 5 Slovakia 3 Slovenia 1 Sweden 10 Switzerland 9 Spain 13 Turkey 65 Ukraine 1 UK 15 Others: Brazil 1 Canada 1 Ghana 1 Egypt 1 Nigeria 2 Somalia 1 USA 1

7 Study population 6033 patients on study days 152 hospitals (42 took part in both studies) 727 patients with NAUTI

8 CDC Definitions for NAUTI 1. Symptomatic UTI: symptoms AND bacteriuria two of 7 criteria indicating UTI 2. Asymptomatic Bacteriuria: indwelling urinary catheter present no indwelling urinary catheter present 3. Other infections of the urinary tract: positive culture of fluid (other than urine) or tissue abscess or other evidence of infection two of 5 criteria indicating other infection Garner et al 1988 Am J Infect Control 16:

9 Prevalence of NAUTI Prevalence in PEP-study 10% 322 cases in 3124 hosp. patients Prevalence in PEAP-study 14% 401 cases in 2909 hosp. patients Prevalence in combined analysis 11% 528 cases in 4662 hosp. patients

10 Clinical presentation of NAUTI ABU 33 Pyelon. Cystitis Urosepsis 11 Other % of total

11 Indications for antibiotics Average urological patient population % of total % of patients are receiving antibiotics Prophylaxis Proven UTI Suspected UTI 6 Other

12 Characteristics of patients with NAUTI Risk factors Urinary catheter 74% Average catheter duration 6-11 days Urinary tract obstruction 49% Previous UTI 44% Antibiotics during previous 3 mo 46% Hospitalisation in previous 6 mo 45% Urinary stones 20%

13 Pathogens causing NAUTI E coli Pseudomonas Klebsiella Enterocooci Proteus Staphylococci Enterobacter Candida Others % of total

14 Use of antibiotics when NAUTI was diagnosed (n=207) 100% Others 80% Aminoglykoside Imi-/meropenem 60% Ceftazidim 40% Cefotax/ceftriaxon 2. Gen. Ceph. 20% Am/ampi+BLI 0% Others Germany Hungary Turkey Russia Cipro-/ofloxacin Co-trim/Trim Nitrofurantoin

15 E. coli Ciprofloxacin (n=132) Resistant Intermediate Sensitive 100% 80% 60% 40% 20% 0% Germany Hungary Russia Turkey Others

16 There is a clear correlation between Antibiotic Consumption and Antibiotic Resistance Björn Wullt

17 Jul 00 Jul 98 Jul 99 Jul imipenem resistance (%) Pseudomonas aeruginosa imipenem consumption (DDDs) A --- consumption resistance resistance Lepper et al 2002 AAC 46:

18 Antibiotic resistance depends on the environment Hygienic factors Selective antibiotic pressure Spontaneous mutations - genetic uptake Survival and spread of Björn Wullt resistant clones

19 Material and Methods 12 months 1996/7 urine isolates from all hospitalised urological patients pathogen: identification pathogen: susceptibility test pathogen: typing Wagenlehner et al 2002 IJAA 19:

20 Results 144 patients 250 urine isolates

21 Clonally related urine isolates cultured from different patients * Species N / Isolates % Gramnegatives 76/ %*

22 Origine of NAUTI NAUTI is mainly catheter related Transmission/cross infection plays a major role in pathogenesis of NAUTI NAUTI is often a biofilm infection

23 Experimental Setup of Catheterassociated Infection Model Goto et al 1999 IJAA 11:

24 Scanning Electron Micrograph of P. aeruginosa No. 02 Biofilm Formed on a Teflon Catheter in Artificial Urine Goto et al 1999 IJAA 11:

25 Teflon Catheters and Biofilmformation Pre. 4th 8th day Goto et al 1999 IJAA 11:

26 Time-kill Courses of Piperacillin and Ceftazidime Against Biofilm Cells of P. aeruginosa No. 02 in Artificial Urine Viable cell counts Piperacillin Viable cell counts Ceftazidime hours PIPC 128 MBC PIPC 32 MBC PIPC 4 MBC PIPC 1 MBC Goto et al 1999 IJAA 11: hours CAZ 64 MBC CAZ 32 MBC CAZ 16 MBC CAZ 4 MBC CAZ 1 MBC

27 Time-kill Courses of Papipenem and Amikacin against Biofilm Cells of P. aeruginosa No. 02 in Artificial Urine Papipenem 10 8 Amikacin Viable cell counts Viable cell counts hours PAPM 64 MBC PAPM 16 MBC PAPM 4 MBC PAPM 1 MBC hours AMK 128 MBC AMK 32 MBC AMK 4 MBC AMK 1 MBC Goto et al 1999 IJAA 11:

28 Time-kill courses of Ciprofloxacin and Levofloxacin against biofilm cells of P. aeruginosa No. 02 in artificial urine Viable cell counts Ciprofloxacin Viable cell counts Levofloxacin hours CPFX 64 MBC CPFX 32 MBC CPFX 16 MBC CPFX 8 MBC CPFX 4 MBC CPFX 1 MBC CPFX 0.5 MBC hours Goto et al 1999 IJAA 11: LVFX 32 MBC LVFX 16 MBC LVFX 4 MBC LVFX 1 MBC LVFX 0.5 MBC

29 unknown Urinary tract Gastrointestinal tract Respiratory tract Skin/ soft tissue Biliary tract Reproductive system others 80% 70% 60% 50% 40% 30% 20% 10% 0% 612 episodes of Gram-Negative Bacteremia total fatal Kreger et al 1980 Am J Med 68:

30 Natural history of SIRS Mortality (%) 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% SIRS sepsis severe sepsis septic shock SIRS sepsis severe sepsis septic shock Rangel-Frausto MS, JAMA 1995

31 Treatment of urosepsis Supportive intensive therapy As early as possible (first hours)

32 Treatment of urosepsis Supportive intensive therapy Empiric antibiotic therapy As early as possible (first hours)

33 Mortality Impact of Inadequate Therapy Severe sepsis and septic shock Garnacho-Montero Harbarth MacArthur Adequate Inadequate Dhainaut F. Scaglione 2007 Garnacho-Montero, et al. Crit Care Med 2003;31: ; Harbarth, et al. Am J Med 2003;115: ; MacArthur, et al. Clin Infect Dis 2004;38: ; Dhainaut, et al. Crit Care Med 2003;31:

34 Empiric antibiotic therapy of bacteremic UTI and clinical success 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% adequate initial AB therapy P = not adequate initial AB therapy total Deaths Elhanan G, Salhat M, Raz R, J Infect 1997

35 Treatment of urosepsis Supportive intensive therapy Empiric antibiotic therapy Specific urological therapy As early as possible (first hours)

36 /SG IV Pyelography

37 /SG IV Pyelography

38 /SG Retro Pyelography

39 Urosepsis Pathogens Escherichia coli other Enterobacteriaceae after urological interventions multiresistant pathogens: Pseudomonas sp. Proteus sp. Serratia sp. Enterobacter sp. Empiric Treatment Cephalosporine 3a, 3b + Aminoglykoside Fluorchinolone* Piperacillin / BLI Carbapeneme *with high renal elimination BLI = beta-lactamase inhibitor Duration of therapy: 3-5 days after defeverescence or elimination of complicating factors EAU guidelines updated 2007

40 Urosepsis following ESWL 84 year male patient Urol. Diagnosis: nephrolithiasis both kidneys ESWL left kidney one week before (no culture before ESWL!) Physical exam: fever (39.4 C), chills, pain left CVA Laboratory: Urinalysis: Leuco 16.6/nl; Creat. 1,76 mg/dl; CRP 23.1 mg/dl ph 5.0; protein 30 mg/dl; Nitrit: negative; Leuco 70/μl; Ery 80/μl Urine culture:?

41 Hospital St. Elisabeth Dpt. Radiology 1 week after ESWL

42 Urosepsis following ESWL 84 year male patient First step therapy: intensive medicine piperacillin/tazobactam 3x4.5 g JJ-stent left ureter Patient remains unstable no improvement of sepsis Next step therapy (within 12 hours): nephrectomy left kidney recovery after several days of intensive care

43 Hospital St. Elisabeth Dpt. Radiology 1 week after ESWL

44 Urosepsis following ESWL 84 year male patient Urine culture: Enterococcus faecalis (10 6 /ml; mono culture) susceptible to all usual antimicrobials

45 Urosepsis - Conclusion Early diagnosis Rapid interdisciplinary approach Early effective antibiotic therapy (dosage!) Early intensive care treatment Early urological treatment Prevention of nosocomial UTI

46

47 International Society of Chemotherapy for Infection and for Cancer 66 national and regional societies with about members International Congresses of Chemotherapy Disease Management Symposia Working Groups International Journal of Antimicrobiel Agents

48 International Society of Chemotherapy for Infection and for Cancer Working Groups ISC - Cancer Section ISC - Virology Section ISC - WG Urinary Tract Infections ISC - WG Endocarditis ISC - WG Pharmacokinetics/Pharmacodynamics ISC - WG Catheter related infections ISC - WG Infections in Areas with Limited Resources ISC - WG Antimicrobials of the Future ISC - WG MRSA ISC - WG Infections in ICU

49 Sumit your paper online

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