Antibiotic Prophylaxis in Urologic Procedures: A Review of the CUA Guidelines & Local Epidemiology of Drug Resistance David Hogarth UBC Urology PGY-1 May 24, 2017 Objectives 1. To review the current CUA guidelines on antibiotic prophylaxis for urologic procedures 2. To review the local epidemiology of drug resistance of common uropathogens 3. To discuss current prescribing practices of prophylactic antibiotics 1
Case Study Mr P, 68 yo M, presenting 6 days post TRUS prostate biopsy At ER triage T 39.4 C, HR 136, BP 128/70 Chief complaint feeling generally unwell,fatigued Case Study Mr P, 68 yo M, presenting 6 days post TRUS prostate biopsy At ER triage T 39.4 C, HR 136, BP 128/70 Chief complaint feeling generally unwell,fatigued In ER septic workup initiated Fluid resuscitated with 2 L NS bolus Given IV piperacillin-tazobactam & vancomycin Blood and urine cultures sent 2
Case Study Further history: Took 3 day course of PO ciprofloxacin Day -1, 0, 1 of TRUS prostate biopsy Tolerated procedure well, no complications 5 days post procedure developed malaise/fatigue No other infectioussymptoms PMHx HTN, prostate biopsy 2 yr ago Case Study Initial course in hospital: Vitalsnormalized in ER with fluid resuscitation & IV antibiotics IV piperacillin-tazobactam continued on ward 3
Case Study Initial course in hospital: Vitalsnormalized in ER with fluid resuscitation & IV antibiotics IV piperacillin-tazobactam continued on ward Question to ponder: Could this case study have been prevented? Part 1 CUA Guidelines 4
Need for Guidelines Guidelines for antibiotic prophylaxis in open operative procedures are readily available Many urologic procedures do not utilize skin incisions, instead using approaches including: Transluminal (endoscopic, catheter manipulation) Transrectal (prostate biopsy) Non-invasive (ESWL) Need for Guidelines Urologic infections may arise from: Skin flora Rectal flora Urinary flora Struvite stones Subclinical prostatitis Urethral catheters Ureteric stents 5
Objective of the CUA Guidelines Develop evidence-based guidelines for the following pertinent clinical areas: Transrectal biopsy of the prostate (TRBP) Extracorporeal shockwave lithotripsy (ESWL) Endoscopic stone manipulation procedures (URS & PCNL) Endoscopic procedures excluding stone manipulation (cystoscopy, UDS, TURBT, ureteric stent insertion, & internal urethrotomy) Transurethral resection of the prostate (TURP) Methods Only randomized controlled trials included Excluded patients with known pre-procedural infections Two reviewers independently abstracted data from included trials Disagreements resolved via a third reviewer 6
Methods Databases included in literature search EMBASE (Jan 1980 Oct 2012) MEDLINE (Jan 1950 Oct 2012) Evidenced-based medicine reviews (inception Oct 2012) ACP Journal Club Database of Abstracts of Reviews of Effects Cochrane Central Register of Controlled Trials Health Technology Assessment Cochrane Database of Systematic Reviews National Health Service Economic Evaluation Cochrane Methodology Register Methods Relative risk (RR) was calculated to summarize each trial outcome Antibiotics vs placebo ; or Antibiotics vs no treatment 95% confidence intervals were determined 7
Transrectal Biopsy of the Prostate Based on one systematic review 9 RCTs 3599 patients Transrectal Biopsy of the Prostate Antibiotics compared to placebo: Outcome RR CI (95%) Quality of Evidence Bacteriuria 0.25 0.15 0.42 Moderate Bacteremia 0.67 0.49 0.92 Moderate Fever 0.39 0.23 0.64 Moderate UTI 0.37 0.22 0.62 Moderate Hospitalization 0.13 0.03 0.55 Moderate 8
Transrectal Biopsy of the Prostate Short course (1 day) compared to long course (3 days) of antibiotics: Outcome RR CI (95%) Quality of Evidence Bacteriuria 2.09 1.17 3.73 Moderate Fever 2.84 0.99 6.16 Moderate UTI 1.4 0.73 2.68 Moderate Hospitalization 4.14 0.47 36.46 Low Transrectal Biopsy of the Prostate Single dose compared to multiple doses of antibiotics: Outcome RR CI (95%) Quality of Evidence Bacteriuria 1.98 1.18 3.33 Moderate Fever 2.84 0.99 8.16 Low UTI 1.4 0.73 2.68 Moderate Hospitalization 3.1 0.64 15.06 Low 9
Transrectal Biopsy of the Prostate Oral compared to parenteral (IV/IM) antibiotics: Outcome RR CI (95%) Quality of Evidence Bacteriuria 0.34 0.06 1.93 Moderate Fever 1.8 0.24 13.45 Moderate UTI 0.85 0.27 2.7 Moderate Hospitalization 1.8 0.24 13.45 Low Transrectal Biopsy of the Prostate The bottom line: Prophylactic antibiotics are recommended for all patients Grade of Recommendation A, Level of Evidence IA Single dose or 1 day as effective as 3 days of antibiotics Insufficient evidence to recommend pre-procedure enemas Most studies investigated quinolones, but choice of agent should be based, in part, on local drug resistance patterns Grade of Recommendation D, Level of Evidence IV Consider perirectal culture swabs in patients at high risk of harboring resistant organisms 10
Extracorporeal Shockwave Lithotripsy Based on 8 RCTs involving 940 patients Inclusion criteria adults with sterile urine pre-operatively Outcomes of interest post-operative fever or UTI Extracorporeal Shockwave Lithotripsy 11
Extracorporeal Shockwave Lithotripsy Extracorporeal Shockwave Lithotripsy Antibiotics compared to placebo: Outcome RR CI (95%) P-value UTI 0.76 0.39 1.48 0.42 Fever 0.26 0.06 1.10 0.07 12
Extracorporeal Shockwave Lithotripsy Relative risk of UTI: Extracorporeal Shockwave Lithotripsy Relative risk of fever: 13
Extracorporeal Shockwave Lithotripsy The bottom line: Prophylactic antibiotics do not significantly reduce the risk of UTI or fever; consider in patients at high risk of infectious complications Grade of Recommendation B, Level of Evidence IB High risk: large stone burden, pyuria, history of pyelonephritis, adjunctive procedures (stent placement, nephrostomy insertion) The choice of agent should be based, in part, on local drug resistance patterns Grade of Recommendation D, Level of Evidence IV Endoscopic Stone Manipulation Procedures Based on 4 RCTs involving 448 patients 2 RCTs studied URS; 1 studied PCNL; 1 studied both URS & PCNL 349 patients underwent URS, 99 underwent PCNL Inclusion criteria adults with sterile urine pre-operatively Outcomes of interest post-operative fever or UTI 14
Endoscopic Stone Manipulation Procedures Endoscopic Stone Manipulation Procedures 15
Endoscopic Stone Manipulation Procedures Antibiotics compared to placebo: Outcome RR CI (95%) P-value UTI 0.30 0.15 0.58 < 0.001 Fever 0.38 0.12 1.21 0.10 Endoscopic Stone Manipulation Procedures Relative risk of UTI: 16
Endoscopic Stone Manipulation Procedures Relative risk of fever: Endoscopic Stone Manipulation Procedures The bottom line: Prophylactic antibiotics reduce the risk of UTI, and there is a trend toward reduction in risk of fever Prophylactic antibiotics should be considered in all patients Grade of Recommendation A, Level of Evidence IA The choice of agent should be based, in part, on local drug resistance patterns Grade of Recommendation D, Level of Evidence IV 17
More About URS More About URS Retrospective review of 81 patients undergoing URS All patients received pre-operative antibiotics A subset of patients also received post-operative antibiotics Purpose: evaluate if the addition of post-operative antibiotics reduces UTI s following URS 18
More About URS More About URS 19
More About URS Results: No significant difference between groups (p = 0.1457) Pre-op antibiotics only 2/42 (4.8%) treated for UTI Both developed pyelonephritis Pre-op and post-op antibiotics 4/39 (10.2%) treated for UTI 2 developed urosepsis, 2 developed cystitis More About URS Conclusion: Supports the CUA and AUA guidelines Possible limitations: Small sample size Retrospective design Subject to selection bias No structured antibiotic regimen 20
More About PCNL More About PCNL RCT of 68 patients undergoing PCNL All patients received pre-operative ampicillin & gentamicin Patients randomized to the intervention arm received nitrofurantoin (100 mg PO BID x 7 days) prior to PCNL Purpose: assess the utility of preoperative antibiotics in patients at lower risk of infections complications Low risk negative urine cultures, no other antibiotics within 14 days of PCNL, and no urinary drains present 21
More About PCNL Results: No significant difference between groups (p = 0.49) Control arm 4/34 (11.8%) developed infectious complications Intervention arm 6/34 (17.6%) developed infectious complications Also, no difference between length of hospital stay More About PCNL Conclusion: Supports the CUA and AUA guidelines Possible limitations: Small sample size Only included patients at low risk of infectious complications 22
Endoscopic Procedures Excluding Stone Manipulation Based on 4 RCTs involving 2556 patients 3 RCTs studied UDS; 1 studied cystoscopy 384 patients underwent UDS, 2172 underwent cystoscopy Inclusion criteria adults with sterile urine pre-operatively Outcomes of interest post-operative fever or UTI None reported fever as an outcome Endoscopic Procedures Excluding Stone Manipulation Based on 4 RCTs involving 2556 patients No trials were identified that met inclusion criteria for: TURBT Retrograde pyelography Ureteric stent insertion Internal urethrotomy 23
Endoscopic Procedures Excluding Stone Manipulation Endoscopic Procedures Excluding Stone Manipulation 24
Endoscopic Procedures Excluding Stone Manipulation Antibiotics compared to placebo: Outcome RR CI (95%) P-value UTI 0.42 0.18 1.01 0.05 Endoscopic Procedures Excluding Stone Manipulation Relative risk of UTI: 25
Endoscopic Procedures Excluding Stone Manipulation The bottom line: Prophylactic antibiotics show a strong trend towards reduction in the risk of UTI, no studies assessed the risk of fever Prophylactic antibiotics should be considered in patients at high risk for infectious complications Grade of Recommendation C, Level of Evidence IB The choice of agent should be based, in part, on local drug resistance patterns Grade of Recommendation D, Level of Evidence IV Transurethral Resection of the Prostate Based on one systematic review 28 RCTs involving 4694 patients 26
Transurethral Resection of the Prostate Inclusion criteria: Comparing antibiotic prophylaxis to either placebo or no treatment Sterile pre-operative urine with no signs of UTI Exclusion criteria: Pre-operative temp > 38 C Indwelling catheter Renal dysfunction (Cr > 177 mmol/l) Bladder tumor Allergy/sensitivity to antibiotics Antibiotic therapy within 1 wk prior to TURP Transurethral Resection of the Prostate 27
Transurethral Resection of the Prostate Transurethral Resection of the Prostate Antibiotics compared to placebo/no treatment: Outcome RR CI (95%) Bacteriuria 0.34 0.30 0.40 Bacteremia 0.84 0.71 0.99 Fever 0.25 0.11 0.56 28
Transurethral Resection of the Prostate Adverse events: Reported in 11 RCTs involving 1847 patients 25 total adverse reactions 19 (1.8%) in antibiotic group 6 (0.7%) in control group No serious adverse events reported Transurethral Resection of the Prostate The bottom line: High incidence of adverse events without antibiotic prophylaxis Bacteriuria (23.4%), bacteremia (4.0%), fever (26.9%) Prophylactic antibiotics are recommended for all patients Grade of Recommendation A, Level of Evidence IA Most studies investigated quinolones, but choice of agent should be based, in part, on local drug resistance patterns Grade of Recommendation D, Level of Evidence IV 29
Summary of CUA Guidelines Antibiotics are useful for the prevention of fever and UTIs for most urologic procedures No antibiotic class demonstrated superiority Duration of prophylaxis was not assessed Multiple societies (IDSA, SIS, SHEA) recommend single dose or < 24 hr Lack of reporting of adverse outcomes Local antibiotic stewardship programs should develop preferred prophylaxis regimens AUA Guidelines Lower Tract Procedure Prophylaxis Indicated Antibiotic(s) of Choice Catheter removal Cystoscopy without tissue manipulation Cystoscopy with tissue manipulation Prostate cryotherapy & brachytherapy TRUS prostate biopsy If risk factors present If risk factors present All patients Uncertain All patients Fluoroquinolone or TMP-SMX Fluoroquinolone or TMP-SMX Fluoroquinolone or TMP-SMX 1 st gen. cephalosporin Fluoroquinolone or 1 st /2 nd /3 rd gen. cephalosporin 30
AUA Guidelines Risk Factors AUA Guidelines Upper Tract Procedure Prophylaxis Indicated Antibiotic(s) of Choice Shockwave lithotripsy Ureteroscopy Percutaneous nephrolithotripsy If risk factors present All patients All patients Fluoroquinolone or TMP-SMX Fluoroquinolone or TMP-SMX 1 st /2 nd gen. cephalosporin or Aminoglycoside with metronidazole/clindamycin 31
Part 2 Local Resistance Patterns Part 2 Local Resistance Patterns www.bugsanddrugs.org 32
Common Antibiotics Ciprofloxacin: Class Time to Peak Half Life Pregnancy Risk Cost per dose 2 nd generation fluoroquinolone Bactericidal 30 min 2 hr 3 5 hr C 500 mg PO = $0.70 400 mg IV = $30.08 Common Antibiotics Co-trimoxazole (trimethoprim-sulfamethoxazole, TMP-SMX): Class Time to Peak Half Life Pregnancy Risk Sulfonamide Bacteriostatic 1 4 hr 6 12 hr D Cost per dose 160mg/800mg PO = $0.12 33
Common Antibiotics Cefazolin: Class Time to Peak Half Life Pregnancy Risk 1 st generation cephalosporin Bactericidal 5 min 1.8 hr Cost per dose 2 g IV = $6.46 B Common Antibiotics Gentamicin: Class Time to Peak Half Life Pregnancy Risk Aminoglycoside Bactericidal 30 min 2 hr Cost per dose 2 mg/kg IV = $27.22 D 34
Common Antibiotics Clindamycin: Class Time to Peak Half Life Pregnancy Risk Lincosamide Bacteriostatic 1 hr 3 hr Cost per dose 600 mg IV = $14.62 B Local Antibiogram Susceptibilities Common Bacteria Susceptible to ciprofloxacin Staph aureus (MSSA) 84% Staph aureus (MRSA) 8% Coagulase ( ) Staph sp. 61% Enterococcus faecalis 54-69% Escherichia coli 73-78% Klebsiella pneumoniae 89-92% Proteus mirabilis 80% Pseudomonas aeruginosa 84-87% 35
Local Antibiogram Susceptibilities Common Bacteria Cipro Staph aureus (MSSA) 84% Staph aureus (MRSA) 8% Coagulase ( ) Staph sp. 61% Enterococcus faecalis 62% Escherichia coli 76% Klebsiella pneumoniae 91% Proteus mirabilis 80% Pseudomonas aeruginosa 86% Local Antibiogram Susceptibilities Common Bacteria Cipro Susceptible to co-trimoxazole Staph aureus (MSSA) 84% 93-95% Staph aureus (MRSA) 8% 90-93% Coagulase ( ) Staph sp. 61% 47% Enterococcus faecalis 62% 0% Escherichia coli 76% 70-74% Klebsiella pneumoniae 91% 82-83% Proteus mirabilis 80% 71-77% Pseudomonas aeruginosa 86% 0% 36
Local Antibiogram Susceptibilities Common Bacteria Cipro Septra Staph aureus (MSSA) 84% 94% Staph aureus (MRSA) 8% 92% Coagulase ( ) Staph sp. 61% 47% Enterococcus faecalis 62% 0% Escherichia coli 76% 72% Klebsiella pneumoniae 91% 83% Proteus mirabilis 80% 74% Pseudomonas aeruginosa 86% 0% Local Antibiogram Susceptibilities Common Bacteria Cipro Septra Susceptible to cefazolin Staph aureus (MSSA) 84% 94% 100% Staph aureus (MRSA) 8% 92% 0% Coagulase ( ) Staph sp. 61% 47% 33% Enterococcus faecalis 62% 0% 0% Escherichia coli 76% 72% 83% Klebsiella pneumoniae 91% 83% 83% Proteus mirabilis 80% 74% 46% Pseudomonas aeruginosa 86% 0% 0% 37
Local Antibiogram Susceptibilities Common Bacteria Cipro Septra Ancef Staph aureus (MSSA) 84% 94% 100% Staph aureus (MRSA) 8% 92% 0% Coagulase ( ) Staph sp. 61% 47% 33% Enterococcus faecalis 62% 0% 0% Escherichia coli 76% 72% 83% Klebsiella pneumoniae 91% 83% 83% Proteus mirabilis 80% 74% 46% Pseudomonas aeruginosa 86% 0% 0% Local Antibiogram Susceptibilities Common Bacteria Cipro Septra Ancef Susceptible to gentamicin Staph aureus (MSSA) 84% 94% 100% Staph aureus (MRSA) 8% 92% 0% Coagulase ( ) Staph sp. 61% 47% 33% Enterococcus faecalis 62% 0% 0% Escherichia coli 76% 72% 83% 89% Klebsiella pneumoniae 91% 83% 83% 94-95% Proteus mirabilis 80% 74% 46% 90% Pseudomonas aeruginosa 86% 0% 0% 94-99% 38
Local Antibiogram Susceptibilities Common Bacteria Cipro Septra Ancef Gentamicin Staph aureus (MSSA) 84% 94% 100% Staph aureus (MRSA) 8% 92% 0% Coagulase ( ) Staph sp. 61% 47% 33% Enterococcus faecalis 62% 0% 0% Escherichia coli 76% 72% 83% 89% Klebsiella pneumoniae 91% 83% 83% 95% Proteus mirabilis 80% 74% 46% 90% Pseudomonas aeruginosa 86% 0% 0% 97% Local Antibiogram Susceptibilities Common Bacteria Cipro Septra Ancef Gentamicin Clindamycin Staph aureus (MSSA) 84% 94% 100% 73-82% Staph aureus (MRSA) 8% 92% 0% 46-56% Coagulase ( ) Staph sp. 61% 47% 33% 44-55% Enterococcus faecalis 62% 0% 0% 0% Escherichia coli 76% 72% 83% 89% Klebsiella pneumoniae 91% 83% 83% 95% Proteus mirabilis 80% 74% 46% 90% Pseudomonas aeruginosa 86% 0% 0% 97% 39
Local Antibiogram Susceptibilities Common Bacteria Cipro Septra Ancef Gentamicin Clindamycin Staph aureus (MSSA) 84% 94% 100% 78% Staph aureus (MRSA) 8% 92% 0% 51% Coagulase ( ) Staph sp. 61% 47% 33% 50% Enterococcus faecalis 62% 0% 0% 0% Escherichia coli 76% 72% 83% 89% Klebsiella pneumoniae 91% 83% 83% 95% Proteus mirabilis 80% 74% 46% 90% Pseudomonas aeruginosa 86% 0% 0% 97% More About Ciprofloxacin 40
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Fluoroquinolone-induced Tendinopathy Fluoroquinolone-induced Tendinopathy 42
Fluoroquinolone-induced Tendinopathy 469 unique abstracts reviewed; included 5 case-control studies 6 cross-sectional/case-series studies 5 cohort studies Incidence of tendon injury: 0.08 0.2% Fluoroquinolone-induced Tendinopathy Increased risk of tendon rupture (OR 2.0) Identified risk factors for tendon rupture: Age > 60 yr old (OR 1.1 4.0) Age > 80 yr old (OR 7.4) Concurrent corticosteroid use (OR 5.8 43.2) Possible risk factors (not adequately evaluated): Chronic kidney disease, obesity, dose, and duration of therapy 43
Fluoroquinolone-induced Tendinopathy Systematic review conclusions: Relatively uncommon condition Tendon rupture usually occurs within 1 month of exposure Higher fluoroquinolone doses may be associated with higher risk Case reports describe tendon rupture after single-dose therapy Current literature is problematic Wide spectrum of tendon disease Most studies rely on patient self-reporting Antibiotics & Clostridium difficile 44
Antibiotics & Clostridium difficile 465 unique articles reviewed, included: 6 case control studies 1 cohort study Objective: To determine the association between antibiotic class and the risk of C diff infection in the community Antibiotics & Clostridium difficile Antibiotic Class OR CI (95%) Clindamycin 16.80 7.48 37.76 Cephalosporins & Carbapenems 5.68 2.12 15.23 Fluoroquinolones 5.50 4.26 7.11 Penicillins 2.71 1.75 4.21 Macrolides 2.65 1.92 3.64 Sulfonamides 1.81 1.34 2.43 Tetracyclines 0.92 0.61 1.40 45
Antibiotics & Clostridium difficile Conclusion: Avoidance of high-risk antibiotics in favor of lower-risk antibiotics may help reduce the incidence of C. diff Multiple limitations: Community setting in non-surgical patients Did not include antibiotic dose or duration Antibiotics & Clostridium difficile 46
Antibiotics & Clostridium difficile Retrospective observational study 134 hospitals within the Veteran s Health Administration 468 386 surgical procedures from 12 surgical specialties Main outcome: 30-day postoperative C. diff rate Overall rate = 0.4% Antibiotics & Clostridium difficile Increased risk of post-operative C. diff with multiple classes of preoperative antibiotics (not prophylaxis) 47
Antibiotics & Clostridium difficile Antibiotics & Clostridium difficile Retrospective observational study 52 hospitals within Michigan from July 2012 Sept 2013 35 363 surgical procedures (only Gen Surg, Vascular, and Gyne) Main outcome: 30-day postoperative C. diff rate Overall rate = 0.51% 48
Antibiotics & Clostridium difficile Use of prophylactic antibiotics not independently associated with risk of post-operative C. diff Antibiotics & Anaphylaxis 49
Antibiotics & Anaphylaxis Incidence of all cause perioperative anaphylaxis: 0.025 0.004% Causes: neuromuscular blockers > latex > antibiotics 70% of perioperative anaphylaxis attributed to antibiotics are from penicillins or cephalosporins Overall incidence of anaphylactic penicillin allergy: 0.01% Antibiotics & Anaphylaxis Less than 10% of patients who report a penicillin allergy have an IgEmediated allergy on skin testing 50% lose sensitivity within 5 years 80% lose sensitivity within 10 years Cross reactivity between penicillin and cephalosporins/carbapenems is 2.5% in those with confirmed IgE-mediated penicillin allergy 50
Endocarditis Prophylaxis Endocarditis Prophylaxis American Heart Association, 2007 update Dental procedures: Prophylaxis is recommended only in high risk patients High risk prosthetic cardiac valves, previous endocarditis, some congenital heart disease Gastrointestinal and genitourinary tract procedures: Prophylaxis is not recommended in low or high risk patients 51
Prosthetic Joint Infection Prophylaxis AUA Best Practice Statement (amended 2012): Antibiotic prophylaxis should not be routinely administered in patients with a prosthetic joint Indicated if both present: 1. High risk of hematogenous joint infection within 2 years of joint replacement, immunocompromised state, previous joint infection 2. High risk urologic procedure for bacteremia stone manipulation, upper tract procedure, procedures involving rectum/bowel, indwelling catheter/stent, recent UTI Case Study Revisited Mr P, 68 yo M, septic post TRUS prostate biopsy Remained stable on IV piperacillin-tazobactam 52
Case Study Revisited Mr P, 68 yo M, septic post TRUS prostate biopsy Remained stable on IV piperacillin-tazobactam Blood cultures negative Urine culture positive for E. coli, resistant to ciprofloxacin Discharged home on PO TMP-SMX Acknowledgements Dr Ben Chew Dr Jennifer Grant Medical Director of the Antimicrobial Stewardship Program (ASPIRES) 53
Questions? Procedure TRUS prostate biopsy SWL URS & PNL Cysto, UDS, & TURBT TURP Who should receive antibiotics (single dose or < 24 hr)? All patients Reduce bacteremia, bacteriuria, UTI, fever, & hospitalization No evidence for pre-procedure enemas Consider perirectal swabs in high risk patients Only if risk factors present Large stone burden, associated pyuria, history of pyelonephritis Adjunctive procedures (ureteric stent, nephrostomy tube) All patients Reduce risk of UTI, trend towards reduced risk of fever Only if risk factors present All patients Reduce risk of febrile UTI Questions? Common Bacteria Cipro Septra Ancef Gentamicin Clindamycin Staph aureus (MSSA) 84% 94% 100% 78% Staph aureus (MRSA) 8% 92% 0% 51% Coagulase ( ) Staph sp. 61% 47% 33% 50% Enterococcus faecalis 62% 0% 0% 0% Escherichia coli 76% 72% 83% 89% Klebsiella pneumoniae 91% 83% 83% 95% Proteus mirabilis 80% 74% 46% 90% Pseudomonas aeruginosa 86% 0% 0% 97% 54