Meningitis and UTI

1. Meningitis and UTI

2. Bacterial Meningitis Clinical Syndrome Fever Headache Stiff neck Altered sensorium CSF findings Elevated pressure � >180 mm H2O Elevated WBC � 1000-5000 (>80% PMNs) Elevated protein � usually >500 mg/dl Low sugar � <40 mg/dl

3. Causes of Meningitis - 1986 Streptococcus pneumoniae - 18% Haemophilus infulenzae - 45% Neisseria meningitidis - 14%

4. Bacterial Meningitis - 1995

6. Meningitis and Age1986 vs. 1995

8. Bacterial Meningitis: Trends in Epidemiology Decreased incidence of H. influenzae Increased incidence of penicillin resistant S. pneumoniae Decreased overall incidence

9. Meningitis Complicating Invasive Infection

10. Etiology of Acute Aseptic Meningitis Enterovirus � ECHO 11 Arboviruses St. Louis and West Nile � flaviviruses California group � Bunyavirdae Colorado Tick Fever � Orbivirus Mumps � no parotitis in 40-50% Lymphocytic choriomeningitis Virus Herpesvirus � HSV - 0.5-3.0% aseptic meningitis HIV

11. Factors Contributing to Inflammation in Bacterial Meningitis Bacterial Factors Cell wall components Lipopolysaccharide Outer membrane vesicles Host Factors Prostaglandins IL-1, IL-6, IL-8 TNF Platelet Activating Factor Macrophage Inhibitory Proteins 1 and 2 Leukocyte integrens Endothelial leukocyte adhesion molecules

12. Etiology of Meningitis in Adults 1962-1988

13. Predisposing Factors in 404 Episodes of Meningitis

14. Rate of Nosocomial Meningitis MGH 1962-1968 1962 � 1970 28% 1971 � 1979 45% 1980 � 1988 48% Edmonton (Alberta) Canada 1985 � 1996 13%

15. CSF IsolatesLUMC 9/95 � 7/02

16. Predisposing Factors in Meningitis Complement deficiency Asplenia Recent exposure to someone with meningitis Recent infection � respiratory, otic Travel to areas with endemic meningitis Injection drug use Recent head trauma Otorrhea or rhinorrhea

17. Symptoms and Signs in Patients with Bacterial Meningitis Headache � >90% Fever � >90% Meningismus � >85% Altered sensorium � >80% Kernig�s or Brudzinski�s sign � >50% Vomiting � 35% Seizures � 30% Focal findings � 10-20% Papilledema � <1%

18. Clinical Findings in Community Acquired Meinigitis

22. Toxic Granulation

23. Neurologic Findings in Community Acquired Meningitis

24. CSF Findings in Community Acquired Meningitis

25. Approach to Meningitis Medical emergency � Initiate therapy immediately Bactericidal activity mandatory in subarachnoid space Diminished levels of antibody and complement Antimicrobial therapy requirements Penetration across BBB Concentration within subarachnoid space Activity within the fluid TIMING � Prompt therapy mandatory �standard of care� CT � before LP if Immunocompromised state � HIV infection, therapy, after transplant History of CNS disease � mass lesion, stroke, focal infection New onset seizure (one week Papilledema Abnormal level of consciousness Get blood clutures and institute antimicrobial therapy before CT

26. Time to Sterilisation of CSF After First Dose of Parenteral Antibiotic

27. Meningitis: Treatment and Age

28. Meningitis Therapy � Positive Gram Stain 

29. Pathogen Specific Therapy for Meningitis S. pneumoniae - Ceftriaxone +Vancomycin H. influenzae - Ceftriaxone N. memingitidis - Penicillin G Listeria - Ampicillin + Gentamicin Group B Streptococcus - Penicillin G + Gentamicin Gram neg bacilli - Ceftazidime (Ceftriaxone) + aminoglycoside

30. Resistance of S. pneumoniae to Beta-Lactams at LUMC

31. Therapy of Pneumococcal Meningitis Penicillin is not reliable in treatment of organisms with intermediate resistance, MIC=0.1-1.0 ug/ml Ceftriaxone is not reliable if MIC 0.5 ug/ml or greater Vancomycin should be used with highly resistant strains or cefotaxime resistant isolates Dexamethasone is associated with decreased levels of vancomycin and ceftriaxone in CSF Use vancomycin + ceftriaxone + rifampin with known or suspected high level resistance

32. Dexamethasone in Bacterial Meningitis Meta-analysis suggests that Dexamethaxone 0.15 mg/Kg Q6H for four days protects against neurological sequellae, esp. hearing loss AAP recommends its use in childhood meningitis Impairs CSF penetration of vancomycin in some studies CONTROVERSIAL in adults

33. Dexamethasone in Bacterial Meningitis

34. Duration of Therapy in Bacterial Meningitis

35. Mortality Meningitis

36. Urinary Tract Infection April 3, 2007 Paul O�Keefe, M.D.

37. Definitions UTI Bacteriuria=bacteria in the urine Significant bacteriuria=numbers of bacteria in voided urine that exceed numbers usually due to contamination, i.e. >105/ml Cystitis � infection of the bladder characterized by dysuria, frequency, urgency and suprapubic pain

38. Definitions UTI II Urethritis � infection confined to urethra and characterized by dysuria and mucoid or purulent discharge from the urethral meatus Acute pyelonephritis � infection in kidney characterized by flank pain/tenderness and fever, often associated with dysuria, urgency and frequency Rigorous � above plus significant bacteriuria and acute infection in the kidney

39. UTI � Route of Infeciton Ascending Gut flora reach bladder via urethra Perineal/periurethral colonization in females Massaging action of intercourse in females/?males Catheterization or other instrumentation Hematogenous Lymphatic

40. Pathogenisis of UTI

41. Host Factors in Susceptibility to UTI I Behavior � frequency of sexual intercourse, use of spermicide-containing contraceptive Susceptibility to local colonization Receptor density Local antibody pH � Vaginal flora Nonsecretors of ABO blood group antigens Inhibition of urine Flushing mechanism Instrumentation

42. Host Factors in Susceptibility to UTI III Obstruction � extra- and intrarenal Pregnancy Weight of uterus Smooth muscle relaxation Neurologic function Systemic antibody?

43. UTI Prevalence by Age and Sex

44. Organisms Urinary Tract Infection Acute uncomplicated E coli � 80% Staph saprophyticus � 5-15% Klebsiella Proteus Miscellaneous Complicated or Recurrent E. coli Proteus Providentia Klebsiella Pseudomonas Serratia Enterococcus Staphylococcus Yeast

45. Cystitis: Clinical Features Acute onset dysuria, urgency, frequency Suprapubic pain and tenderness Young sexually active women Hematuria � 50% Pyuria Positive cultures Lower numbers may be significant

46. Major Causes of Acute Dysuria in Women Cystitis � E. coli, S. saprophyticus, Proteus species, Klebsiella species Urethritis � STD�s: N. gonorrhoeae, C. trachomatis, HSV Vaginitis � Candida, Trichomonas vaginalis, normal vaginal flora (BV)

47. Clinical Features of Conditions Causing Acute Dysuria in Women

48. Acute Cystitis in Men Uncomplicated Rare � 5-8 per 10,000 Risk Factors Homosexual Intercourse with urinary tract-infected female Lack of circumcision Treatment T/S or fluoroquinolone Seven days

49. Complicated Cystitis Pregnancy Extremes of age Diabetic Immunocompromised Multiply treated Urinary catheter-associated Spectrum Healthy woman Hospitalized with neurogenic bladder Indwelling bladder catheter

50. Pyelonephritis: Clinical Features Acute flank pain, nausea/vomiting, fever, lower tract symptoms Costovertebral tenderness Bacteremia and septic shock Complicated � papillary necrosis Diabetes, SS disease, Obstruction Risk increased in pregnancy White blood cell casts

51. Hospitalization in Pyelonephritis Inability to maintain oral intake or take medications Concerns about compliance Uncertain diagnosis Severe illness: high fever, pain, debility, shock

52. Prostatitis: Clinical Features Perineal and lower back pain Acute Fever, chills, dysuria, urinary retention Boggy, tender prostate Chronic Asymptomatic or Perineal pain or Mild dysuria Urine cultures positive Nonbacterial prostatitis � 90%

53. Specimen Collection Clean-voided, midstream urine Catheterization Suprapubic aspiration

54. Instructions for Patient Remove underpants completely so they will not get soiled. Sit comfortably on the seat, but do not leave your knees in front of you. Instead swing one knee to the side as far as you can. Spread yourself with one hand, and continue to hold yourself spread while you clean and collect the specimen. Wash�Be sure you wash well and rinse well before you collect your urine sample. Wash only the area from which you pass urine. You do not have to wash hard, but wash slowly. Be sure to wipe from the front of your body towards the back. Wash between the folds of skin as carefully as you can. Do not put sponges in the toilet. Put them back in the plate. Rinse�After you have washed with each soap pad, rinse with each moistened pad with the same front to back motion. Do not use any pad more than once. Hold cup by the outside and pass your urine into the cup. If you touch the inside of the cup or drop it on the floor, ask the nurse to give you a new one.

55. Suprapubic Aspiration

56. Microscopic Urinalysis Pyuria = more than 10 WBC�s/�l (10,000/ml) Centrifuged � more than 2 - 5 WBC�s/hpf Sensitivity 95%; specificity 71% WBC casts � indicate pyelonephritis Gram stain One or more bacteria per oil-immersion field correlates with >105/ml of urine Less sensitive; more specific

57. WBC�s

58. WBC with bacteria

59. WBC Cast

60. Chemical Screening Tests Leukocyte esterase � indicates pyuria Nitrite � detects action of bacterial nitrate reductase on urinary nitrates Comparable sensitivity to urinalysis but false negative tests occur

61. Urine Culture Quantitative urine culture - >105 bacteria/ml usually (80% correlation) indicates infection Less than 1000 (103) bacteria/ml usually indicates contamination Lower numbers, i.e., 102-104/ml, may be significant in young women with cystitis, males, and patients with indwelling catheters Blood culture � positive in acute pyelonephritis, prostatitis

65. General Statements about Treatment of UTI Treat symptomatic patients regardless of age Children and pregnant women are likely to benefit from therapy Bacteriuric hospitalized patients have higher mortality than hospitalized patients without bacteriuria

66. Principles of Antimicrobial Therapy of UTI No evidence to support use of bactericidal agents Disappearance of bacteriuria correlates with sensitivity of organism to levels of drug achieved in urine May not get adequate levels in renal failure, e.g. aminoglycosides Objective of therapy � eliminate bacteriuria Response Cure Persistence Relapse Reinfection

67. Treatment of Acute Cystitis Three day course of Trimethoprim/sulfamethoxazole Quinolone Nitrofurantoin � 7 days Follow up studies not necessary

68. Diagnosis and Treatment of Complicated Cystitis Obtain urine culture in addition to urinalysis Empiric treatment should be broad spectrum and well tolerated Ciprofloxacin or levofloxacin Ceftriaxone, aminoglycoside once daily Alter therapy based on culture Treat for 7-14 days

69. Treatment of Pyelonephritis Acute pyelonephritis � uncomplicated Trimethoprim/sulfamethoxazole or quinolone 14 days of therapy (7 days ciprofloxacin) Alter therapy based on culture results Hospitalized Ceftriaxone or aminoglycoside Enterococcus � ampicillin plus gentamicin Ciprofloxacin, ofloxacin, levofloxacin Septic shock or treatment experienced Ceftazidime + gentamicin Oral when improved

70. Follow up Pyelonephritis Follow up cultures After 48 hours � SHOULD BE STERILE 14 days after completion of therapy in order to detect relapse Not indicated in recent recommendations Recurrence of symptoms Repeat culture and susceptibility Same organism � consider US or CT Retreat with two-week regimen

71. Urinary Catheter Risk

72. Catheter-associated Urinary Tract Infection Prevention Avoid unnecessary catheterization Remove catheter as soon as possible Coated catheters effective in certain situations Treatment � patients with indwelling catheter Do not Screen or treat asymptomatic Change catheter when obtaining culture Or use port Empiric based on Gram stain, previous culture, epidemiology 14 days less relapse than 3 days in one SCI study Screen 48 h after removal of short term and treat

73. Prevention of Recurrent UTI Behavioral Change contraception method Post-coital voiding, liberal fluid intake Cranberry juice Antimicrobial Continuous: T/S, nitrofurantoin, cephalexen, ciprofloxacin Post-coital: Same as above Intermittent self-treatment Less total antibiotic than 1 or 2.

74. Case: 48 yo man from SCI Unit transferred to MICU with fever and hypotension. Previously had Pseudomonas resistant to gent, cipro, ceftriaxone What specimens would you obtain? What antibiotics would you start What would you do at this point?