Transcription

1 Honeymoon cystitis and prostatitis that lingers on 1

2 28 year-old. Just married Honey-moon trip to Kenya 2

3 28 year-old. Just married D2: Dysuria, frequency, supra-pubic discomfort D3: manage to get a doctor Dx: Honey-moon cystitis Px: co-trimoxazole Two more attacks in the next 2 months Urine: E. coli (S to co-trimoxazole, levofloxacin) Symptoms free between attacks Symptoms onset bear relation to SEX 3

4 Seek your advice 1. Abstinence from sex 2. USS bladder, ureters, kidney 3. Give prophylactic antibiotic 4. Change to levofloxacin 5. All of the above One best way to reduce recurrence 4

5 To recur UTI To err is human Alexander Pope 5

6 Recurrence: part of natural course in UTI UK GP database, Women, aged 15-44yr Recurrence/Re-Treatment necessary in 15% within 4 weeks, irrespective of initial choice/antibiotic duration 6

7 Frequent (1 per mth) recurrence in 1% 7

8 Urological evaluation Routine: not cost-effective Unlikely to reveal abnormality Indicated if recurrent plus: Haematuria between infections Pyelonephritis Urea-splitting bacteria (Proteus spp.) Urinary stones/obstructive symptoms Severe diabetes 8

9 Why recurrent in some women? Host-microbe match most important Bad bacteria - adherent strains Unfortunate host - receptive epithelium Estrogen deficiency in postmenopausal women Bacterial persistence in fecal reservoir within bladder mucosa Mulvey MA et al. PNAS 2000;97: Manges AR et al. NEJM 2001;345(Oct):1007

10 10 Anderson et al Science 2003

11 11

12 Prevention of recurrent UTI in women Useful Prophylactic antibiotics Cranberry juice Avoid spermicidecoated condoms Doubtful Behavioral changes (pre-/post-coital voiding patterns, urination frequency, wiping patterns, use of hot tub, use of pantyhose or tights) Acupuncture (1 RCT) Avoid exaggerated genital hygiene (vaginal douching or lotion, deodorant spray Damage to physiological vaginal flora facilitate UTI 12

13 Distribution of urine isolates DH Sentinel surveillance Year 2001 Agent % (n=471) E. coli 73% Staphylococci 4.2% Enterococcus 5% Klebisella spp. 5.5% Others

14 If a 28yr-old female outpatient presents to my clinic with uncomplicated cystitis 1. Ampicillin today, I will treat with 2. Cotrimoxazole (Septrin) 3. Levofloxacin (Cravit) 4. Amoxicillin-clavulanate (Augmentin) 5. Nitrofurantoin 14

15 Response by attending PDipID course Nitrofurantoin 24% Ampicillin 10% Great majority (56%) choose Ampicillin Cotrimoxazole Fluoroquinolone Cotrimoxazole 20% Augmentin 20% Levofloxacin 26% Nov

16 What about our GPs? Ciproxin Levofloxacin Ofloxacin Norfloxacin Self-reporting survey 45 GPs 98 episodes of UTI TP Lam & PL Ho et al Augmentin Zinnat Cedax 16

17 14.7% Outpatients with UTI 13 Private lab 17 Ho PL Diagn Microbiol Infect Dis 2007; Ho PL J Antimicro Chemother 2007

18 18 Ho PL Diagn Microbiol Infect Dis 2007; Ho PL J Antimicro Chemother 2007

19 Rate of ESBL-producers Ho PL Diagn Microbiol Infect Dis 2007; Ho PL J Antimicro Chemother

20 Empirical therapy failure rates (if pathogen is E. coli) If resistance in vitro resistant = 100% in If therapy fail in 50% of all vivo resistance resistant infections Amoxil 1 in 2 Amoxil 1 in 4 Septrin 1 in 3 Septrin 1 in 6 Fluoroquinolone 1 in 5 Fluoroquinolone 1 in 10 Nitrofurantoin 1 in 50 Nitrofurantoin 1 in 100 Fosfomycin 1 in 250 Fosfomycin 1 in 125 Treatment Goal: >90% bacteriuria eradication 20

21 Acute uncomplicated bacterial cystitis Single dose: lower cure rates, more recurrences (Exception: Fosfomycin) 3 d = 7 d for co-trimoxazole, trimethroprim, fluoroquinolones Nitrofurantoin: 7 d more effective than 3 d ß-lactams: lower eradication rates, slightly more recurrences; more S/E Warren JW et al. CID 1999;29:745 21

22 Uncomplicated UTI in woman Treatment Freq. Length Cost Failure rate (likely) 1. Nitrofurantoin Qid 5-7d HK$2.8 <2% 2. Amoxil 3. Septrin TDS BD 5-7d 3d HK$3.8 HK$5.2 30% 15%-25% 4. Augmentin TDS 5-7d HK$14 <2% 5. Ciprofloxacin 5. Levofloxacin BD QD 3d 3d HK$29 HK$29 8%-18% 8%-18% Fosfomycin 1 dose 1 dose HK$68 <1% 22

23 Pyridium (Phenazopyridine) Urinary analgesic Not an antibiotic Do not use for >2 days 90% renal excretion/ oxidative chemical Avoid in renal impairment/ G6PD Hemolysis, acute renal failure, hepatotoxicity, pancytopenia 23

24 Long term prophylaxis Does not alter the natural history of recurrent infections. Fractionally extracts patients into longterm remission. 1/4 therapeutic dose TMP, TMP/SMZ, & nitrofurantoin are equally effective despite different modes of actions 24

25 Nitrofurantoin in prevention of recurrent cystitis 219 females given nitrofurantoin for 1 yr 50 vs. 100 mg QD vs. BD Efficacy: recurrence by 80% Breakthrough: half by nitro-s strains Side effects: nausea (13%), serious (none) Macrocrystal fewer nausea equally effective fecal flora: no overgrowth by nitro-r JAC 1998;42:363 25

26 Some practical tips Explaining what is to happen. Start prophylaxis ASAP after sterilizing urine. Withhold during breakthrough. Resume after therapy. Dispensing at intervals. Encouraging patients with minor GI side effects. 26

27 Does this fruit works? Cranberry 小紅莓 27

28 Summary of prospective studies with >100 subjects Study Stother (RCT) Kontiokari Dignam Avorn (RCT) Year women 20% with recurrent UTI women 16% with recurrent UTI Cranberry juice 小紅莓汁 Population 538 OAH residents 153 elderly women (bacteriuria) Cranberry 20 cases per month 15% Placebo/ Control 32% 36% 27 cases per month (historic) 28% 28

29 Cranberry juice 小紅莓汁 How it work? Anti-adhesins Fructose 果糖 Proanthocyanidin 花青素原 Blocks adherence Selects for less adherent strains Safety Slight laxative effect Cranberry concentrate increase urine excretion of oxalate 草酸 (? Risk of stone formation if long term) Terris et al Urology

30 Two years later 45-yr-old husband. Good past health 3-day history of dysuria & frequency Treated with oral levofloxacin for 7 days MSU = E. coli, sensitive to cotrimoxazole, levofloxacin, cefuroxime, augmentin, gentamicin Another attack 2 months later MSU again = E coli PR: prostate normal finding 30

31 What investigation is most likely to yield diagnostic information? 1. Transrectal Ultrasound (TRUS) prostate 2. Ultrasound kidney, bladder, ureters 3. Check PSA 4. The Stamey s test 5. I don t know 31

32 What investigation is most likely to yield diagnostic information? 1. Transrectal Ultrasound (TRUS) prostate (2.8%) 2. Ultrasound kidney, bladder, ureters (58.3%) 3. Check PSA (8.3%) 4. The Stamey s test (19.4%) 5. I don t know (11.1%) 32

33 Chronic bacterial prostatitis Relapsing UTI by the same organism Positive 4 or 2 glass test Accepted pathogens E. coli (up to 70%) Other Enterobacteriaceae Pseudomonas aeruginosa Enterococci Tx 6-12 wk antibiotics Doubtful candidates S. epidermidis Chlamydia trachomatis Mycoplasma genitalium Ureaplasma urealyticus Associated conditions Retrograde spread of bacteria into prostatic ducts Dysfunctional voiding Previous instrumentation 33

34 Stamey s technique 4 glass Prostatitis NG NG Sterilize MSU with Nitrofurantoin, or Augmentin 1Log higher count 10 3 cfu/ml 10 2 cfu/ml E. coli Difficult to perform Limited sensitivity for Gram-pos 34

35 Semen 2 glass Repeat if ejaculate yield Gram positive bacteria Prostatitis NG cfu/ml E. coli Sterilize MSU with Nitrofurantoin, or Augmentin 1Log higher count Easier to perform Better sensitivity for Gram-pos 35

36 Antibiotic concentration in prostate Best penetration for lipophilic, non-ionized and small chemicals GOOD (site level >100% serum) Fluoroquinolone Trimethoprim (Septrin) Rifampicin Tetracyclines, esp minocycline Macrolides (erythromycin inactivated by acid) MODERATE Beta-lactams 14-65% of serum concentration Sulphonamides 50%, fluconazole 30% Aminoglycosides 50% (not active in acid environment) MINIMAL/NEGLIGIBLE Nitrofurantoin Fosfomycin Vancomycin/teicoplanin Chloramphenicol 36

37 UTI When to culture? Uncertain diagnosis Relapse Recurrent infection No response to antibiotic Postmenopausal women Male patient 37

38 Thank you 38

39 Inferring bacteriuria from urinalysis: Nitrite detection Some bacteria including the lactose positive Enterobactericeae, Staphylococcus, Proteus, and Psuedomonas are able to reduce nitrate in urine to nitrite. Principle: Nitrite react with substrates in strip to produce a pink color Negative test may not reliable ruled out UTI because: Some bacteria (e.g. enterococcus) do not have the enzyme for reducing nitrate to nitrite Urine may not be retained in the bladder for long enough for bacteria to reduce nitrate (e.g. presence of urinary catheter, frequent voiding) 39

40 Inferring pyuria from urinalysis: esterase Leukocyte esterase is used as an indicator of leukocyte in urine. Principle: leukocyte esterase react with substrates in strip to produce a purple color Limitations Some drugs (e.g. cephalexin, high glucose level) may interfere with chemical reaction leading to false negative results Positive result may occur from contamination of specimens by vaginal discharge 40