Curriculum Vitae Nama : Dr. Sudung O. Pardede, Sp.A(K) Pekerjaan : Staf pengajar Divisi Nefrologi,

Departemen Ilmu Kesehatan Anak FKUI-RSCM, Jakarta

Riwayat pendidikan: 1982 : dokter umum : FK UKI 1992 : dokter spesialis anak : FKUI 2002 : dokter spesialis anak konsultan : FKUI

Riwayat pekerjaan: 1983 : dokter RSUP Pekanbaru, Riau 1984 1989 : Kepala Puskesmas Kec. Langgam,

Kabupaten Kampar, Riau 1993 sekarang : staf pengajar Departemen IKA FKUI RSCM 1997 : fellow nefrologi di Academisch Ziekenhuis Njimegen,

Nederland 1999 2002 : sekretaris III PP IDAI 2002 2008 : sekretaris I PP IDAI 2008 sekarang: sekretaris umum PP IDAI 1999 sekarang: bendahara KAMAS

Sudung O. Pardede

Department of Child Health Faculty of Medicine University of Indonesia Cipto Mangunkusomo Hospital

Jakarta

A common health problem

Cumulative incidence: 2%-8% by 10 years UTI: sign of urinary tract abnormalities Cause ESRD Uncomfort symptoms Unexplained fever in neonates

Definition

Condition in which there is growth of bacteria within the urinary tract in significant number

Renal parenchymal infection Lower urinary tract infection

Complications

Short term problems Acute kidney injuri (AKI) Urosepsis Scar formation

Long-term sequela of renal scarring Hypertension Proteinuria Progressive-related complications to ESRD Pregnancy-related complications Smellie JM. Clinical Paediatric Nephrology, 1994, p.160-74 Lamber H, Coulthard M. Cilical Paediatric Nephrology, 2003,197-226

Wong SN. Practical Paediatric Nephrology, 2005, 160-7.

Clinical manifestations

Vary depends on age, site of infection, severiy of inflammation

Neonates: Non specific Slow weight gain Temperature instability Feeding difficulties Irritability Vomiting Diarrhea Abdominal distention Jaundice Sepsis : 30%

< 1 years: Fever Irritability Sickly appearance Refusal of food Vomiting Diarrhea Abdominal distention Jaundice

Preschool and school aged Dysuria Urgency Increased frequency Enuresis Flank pain Fever, chills Costovertebral tenderness Macroscopic hematuria

American Academic of Pediatrics

2 months - 2 years: unexplained fever: UTI is considered All UTI (particularly with high fever)

considered as pyelonephritis until proven (strength of evidence: strong)

American Academic of Pediatrics, Pediatrics 1999;103:843-1052

Causes of UTI Common: E. coli: 60-92% Other common:

Klebsiella sp. Proteus sp. Enterococcus Enterobacter Acinetobcter

Less common: Psedomonas sp. Group B Streptococcus Staphylococcus aureus and epidermidis Staphylococcus saprophyticus Haemophylus influenzae

Lambert H, Coulthard M. Clinical Paediatric Nephrology, 3rd ed., 2003,p.197-226 Saadeh SA, Ma*oo TK. Pediatr Nephrol 2011

Route of infection

Ascending from urethral orifice bladder Hematogenous route (neonates)

Table : Hosts factors preventing bacterial adherence to uroepithelium Mechanical action of voiding Tamm Horsfall protein Bacterial interference by endogenous periurethral flora Urinary oligosaccharides Spontaneous exfoliation of uroepithelial cells Urinary immunoglobulins Mucopolysaccharide lining of the bladder wall

Table : Hosts factors predisposing to UTI in children

Maternal UTI Lack of breast feeding Receptors for uropathogen Defective bladder mucosal factor Presence of the prepuce Antibacterial eradication of vaginal flora Urinary secretory IgA

Table : Hosts factors predisposing to UTI in children

Anatomic factors: VUR and intrarenal reflux Urinary tract obstruction Foreign body in urinary tract Duplicated collecting system Ureterocele

uroepitelial cell adherence Nonsecretors with blood group antigens

Table. Bacterial factors associated with uropathogenics virulence of E. coli

P-fimbriae Capsul Adhere to uroepithelium Belongs O and K serotype Produce hemolysin Produce colistin V Produce aerobactin Resistant to antibacterial action Ability to grow Rapid doubling time Ability to colonize the gut

Bowel ora

Emergence of uropathogenic strains

Perineal & anterior urethral colonizaFon (vaginal colonizaFon in females)

Normal mucosal defence barries HOST FACTORS 1. Enhanced uroepithelial adherence 2. VUR 3. Intrarenal reux 4. Obstructed urinary tract 5. Foreign body (urinary catheter)

CysFFs

Acute pyelonephriFs

Renal scarring Urosepsis

BACTERIAL VIRULENCE

Fig. Pathogenesis of ascending UTI

Laboratory investigation

Urinalysis:

Leucocyturia: Leucocyte esterase test Nitrite stick tests

Most bacteria that cause UTI produce nitrite Specificity : 90-100%, sensitivity 53% (15-82%)

Bacteria take time to produce nitrite UTI: tends to void more frequent

Hematuria and proteinuria: sensitivity and specificity: low Phase-contrast microscopy: bacteria

Lambert H, Coulthard M. Clinical Paediatric Nephrology, 3rd ed., 2003,p.197-226

Test Sensitivity % (Range)

Specificity % (Range)

Leukocyte esterase Nitrite Leukocyte esterase or nitrite positive Microscopy: WBCs Microscopy: bacteria Leukocyte esterase or nitrite or microscopy positive

83 (67-94) 53 (15-82) 93 (90-100)

73 (32-100) 81 (16-99)

99.8 (99-100)

78 (64-92) 98 (90-100) 72 (58-91)

81 (45-98) 83 (11-100) 70 (60-92)

Table : Sensitivity and specificity or components of the urinalysis alone and combination

1. Methods of urine collection

a. Suprapubic aspiration: gold standard

b. Catheterization: Sensitivity: 95%; Specificity: 99%

c. Mid-stream specimen

d. Urine collector/bag sample: high false positive

2. Interpretation of culture

Depends of method of urine collections and clinical manifestations

Kass criteria: Urine catheterization and mid stream: 100.000 cfu/mL urine Supra-pubic aspiration: any bacteria

Others: urine catheterization: > 50.000 cfu/mL Practically: if bacteria:

> 100.000 cfu/mL : siginificant 10.000 100.000 cfu/mL : doubtfull, must be repeated 1.000 10.000 cfu/mL : contamination < 1.000 cfu/mL : negative. Usually: one strain bacteria. If bacteria > 1 strain: contamination

Complex UTI

UTI with anatomical and functional urinary tract abnormalities which cause stasis of urine:

Vesico-uretero reflux (VUR) Hydronephrosis Urolithiasis Neurogenic bladder, etc)

Acute pyelonephritis UTI in neonate

Definition of atypical UTI and recurrent UTI

Atypical UTI Seriously ill Poor urine flow Abdominal or bladder

mass creatinine Septicaemia Failure to respond to treat

with suitable AB within 48 hours

Infection with non E. coli organisms

Recurrent UTI 2 or more episode of UTI

with acute pyelonephritis or

1 episode of UTI with acute pyelonephritis plus 1 or more episode of cystitis or

3 or more episode of UTI with cystitis

National Institute for Health and Clinical Excellence. (2007):

Management

1. Eradication of acute infection

Depends on: infection location (cystitis vs pyelonephritis) patients age severity of presentation antimicrobial resistance pattern

Empiric therapy should be initiated after urine specimen for culture has been obtained

Elimination of acute infection and prevent urosepsis

Reduce/prevent renal parenchyme damage Lambert H, Coulthard M. Clinical Paediatric Nephrology, 3rd ed., 2003,p.197-226 Saadeh SA, Ma*oo TK. Pediatr Nephrol 2011

Acute pyelonephritis

Hospitalization 10 14 days Parenteral AB maybe replaced by oral AB after 5

days: Patient has improved symptomatically Systemic signs of toxicity have disappeared Patient: afebrile for 48 hours Organisme is sensitive to an orally administered AB

Low dose AB prophylaxis for prolonged period

Cystitis

Oral antibiotics Severe cystitis (pain, vomiting, dehydration):

hospitalization 7-10 days (3-5 days) Trimetoprim-sulfametokszol, nitrofurantoin,

amoxicillin, amoxicillin-clavulanic, cefixime

UTI in neonate

Commonly associated with sepsis IV antibiotics AB: 10 14 days

Table : Some antimicrobials for oral treatment of UTI

Antimicrobial Dosage

Amoxicillin-clav. Sulfonamide TMP in combination with SMX Sulfisoxazole Cephalosporin Cephalexin Cefixime Cefpodixime Cefprozil

20-50 mg/kg/d in 3 doses 6-12 mg TMP, 30-60 mg SMX per kg per d in 2 doses 120-150 mg/kg/d in 4 doses 50-100 mg/kg/d in 3 doses 8 mg/kg/d in 2 doses 10 mg/kg/d in 2 doses 30 mg/kg/d in 2 doses

Table: Some antimicrobials for parenteral treatment of UTI

Antimicrobial Daily dosage

Ceftriaxone Cefotaxime Ceftazidime Cefazolin

Gentamycin Tobramycin Ticarcillin Ampicillin

75 mg/kg/d 150 mg/kg/d 150 mg/kg/d 50 mg/kg/d 7,5 mg/kg/d 5 mg/kg/d

300 mg/kg/d 100 mg/kg/d

2. Detection and treatment (surgery) of functional/anatomical urinary tract

abnormalities

Physical examinations Radiological examinations

Ikatan Dokter Anak Indonesia (IDAI)

UKK Nefrologi

Konsensus ISK pada Anak

2011

Gambar: Algoritme pencitraan pada bayi (< 6 bulan) dengan ISK

Gambar: Algoritme pencitraan pada anak (6 bulan 3 tahun) dengan ISK

Gambar: Algoritme pencitraan pada anak (> 3 tahun) dengan ISK

3. Detection, prevention, and treatment of recurrent infection

Urine culture Treat predisposing factors Prophylaxis

antibiotics probiotics

Prophylaxis treatment Indications:

Children with high risk: obstructive uropathy High grade VUR (The International VUR Study of Children) Recurrent UTI Acute pyelonephritis

Not recommended: first febrile UTI without VUR or with grade I-II VUR routinely for the first UTI

Complex UTI: prophylaxis for 3 - 4 months Children in prophylaxis with reinfection:

Treat with other antibiotic, not to increase the dose

National Institute for Health and Clinical Excellence. (2007): Montini and Hewitt, Pediatr Nephrol 2009;24:1605-9.

Table: Antibacterial prophylaxis for UTI

Trimetoprim :1-2 mg/kgbw/d Co-trimoxazole

Trimetoprim : 1-2 mg/kgbw/d Sulphamethoxazole : 5-10 mg/kgbw/d

Cephalexin : 10-15 mg/kgbw/d Nitrofurantoin : 1 mg/kgbw/d Nalidixic : 15-20 mg/kgbw/d Cefaclor : 15-17 mg/kgbw/d Cefixime : 1-2 mg/kgbw/d

Smellie JM. Clinical Paediatric Nephrology, 1994, p.160-74 Lamber H, Coulthard M. Cilical Paediatric Nephrology, 2003,197-226 Wong SN. Practical Paediatric Nephrology, 2005, 160-7.

manajemen ISK pada anak