Update on Urinary Tract Infections Rakesh Khera
Page numbers followed by f refer to figure and t refer to table.
Ablative surgery 11
Acid-fast bacillus
smear 4
urine cultures 4
Acinetobacter baumannii, carbapenem-resistant 113, 116
Acquired immunodeficiency syndrome (AIDS) 163
Acupuncture 71
Acyl-homoserine lactones 173
Adenosine triphosphate 10
Aldehydes 38
Amikacin 59, 120
Aminoglycosides 42, 119, 120
Ammonia 172
Amphotericin B 23, 60
Ampicillin 59
Amyloidosis 180
Antiadhesion substances 152
Antibiotics 52, 58, 119, 149
Antifungals, systemic 23
Anti-infective catheters, use of 105
coated catheters, use of 62
prophylaxis 71, 69
therapy 57, 58
Antireflux surgery, role of 90
Arteriosclerosis 39
Aseptic technique 62, 89, 101, 103
Aspergillus fumigatus 25
Asymptomatic bacteriuria, catheter-associated 62
Autonephrectomy 8, 195
Azithromycin 148
Azotemia 26
Aztreonam 59, 115
Bacteremia 82, 95, 115
gram-negative 57
nosocomial 57
Bacteria 66, 75, 138
adhesins 167
armor 171
factors 127
interference 150
persistence 66
pili, phase variation of 169
virulence 165, 170
Bacteriophages 151
Bacteriuria 58, 68, 7476, 81, 102
asymptomatic 51, 60, 74, 76, 78, 8083, 89, 95, 99, 161, 170
catheter-associated 51
incidence of 66
significant 160
symptomatic 94
Bacteroides 163
Balloon dilatation 12
Bedaquiline 10
Beta-lactamase inhibitors 42
Biofilm 134, 135
acquire three-dimensional structure 139f
architecture and genesis of 138
bacterial 134
detachment 140
formation steps 139f
infection 147
treatment of 147
maturation 140
phenotype 141
Biopsy 8, 90
Bladder 2, 8, 24, 76
abnormalities, functional 67
biopsy 8
catheterization, prolonged postoperative 87
epithelium 76
filling under direct vision 8
lesions 2
malignancy 33
mucopolysaccharide coating of 76
mucormycosis of 26f
thimble 2, 8
cultures 56
pressure 45
Bloodstream infection 99
Boari flap 12
Bone marrow 114
Bubbly renal parenchyma 40f
Burning micturition 195
Calyces, distorted 8
Calyx, dilated 8
Candida 15, 16, 96
albicans 16, 17, 23, 27, 33, 152, 162
fungemia 77
glabrata 17, 20, 23, 60, 61
krusei 17, 23
parapsilosis 17
pyelonephritis 19
tropicalis 17
urinary tract infection 16
Candidal colonization 19
Candidemia 25
Candiduria 16, 20, 25, 52, 60, 99
Capsular polysaccharide 166
Carbapenem 59, 115, 116, 119, 120
Carbapenemase-producing organisms 59
Carbon dioxide 34, 172
Carcinoma bladder 12
and drainage tubes, disconnection of 62
biofilm, micrograph of 146f
care 101
aseptic 52, 97
early removal of 62
inserter, lower professional training of 97
insertion checklist 106f
insertion of 62
removal 62
replacement 62
Cefepime 59
Ceftazidime 59
Ceftriaxone 59
Cell to cell communication system 143
Cellulose 139
Cephalexin 71
Cephalosporins 42, 119
Cervical immunoglobulin A 75
Chemotherapy 8
Chloramphenicol 119, 122
Chromatography, thin layer 145
Cilastatin 59
Ciprofloxacin 59
Cirrhosis 53
Citrobacter 162
Clarithromycin 148
Closed drainage systems, use of 62
difficile colitis, nosocomial 57
perfringens 163
septicum 33
Coccidioides immitis 16
Coccidioidomycosis 15
Coexisting renal carcinoma 11
Colistimethate 59
Colistin 115
Colonic acid 139
Colony forming units 74, 94, 160
Coma 38
Complex closed drainage systems, use of 62
Computed tomography 41, 179, 183, 186, 193, 196
imaging 190
scan 7, 41
axial image of 222
Confusion 38
Contrast enhanced ultrasonography 182
Cork screw ureter 8
Cowper ducts 182
Cranberry products, use of 62
Cryptococcus neoformans 16
Cystitis 82, 165
cyclophosphamide-induced 180
emphysematous 46, 181f, 196
radiation 180
superficial 12
Cystocele 66, 68
Cystogram 182
Cystoplasty, augmentation 12
Cystoscopy 8
Cystourethrography, micturating 180
Cytomegalovirus 88
Dehydration 112
Deoxyribonucleic acid 5, 165
Diabetes 45, 112
mellitus 19, 32, 52, 67, 75, 87, 97, 114
Diarrhea 120
Diguanylate cyclases 150
Dihydro-nitroimidazooxazole derivative 10
Disseminated intravascular coagulation 42
D-mannose 70
Doripenem 59, 120
Double J stent 44
early removal of 89
placement of 12
Doxycycline 115, 121
Dysreflexia, autonomic 96
Dysuria 3, 38
Empirical initial antimicrobial therapy 42
Endocarditis 95
Enterobacter 68, 162
Enterobacteriaceae 34, 54, 67, 70, 111, 146f
carbapenem-resistant 113, 116
Enterococcus faecalis 126, 152, 162
Enzyme inhibitors 150
Epididymectomy 11
Epididymis 2
Ertapenem 59, 120
Eryptococcus neoformans 33
Erythromycin 148
Escherichia coli 17, 33 46, 54, 67, 68, 76, 87, 96, 111, 117, 120, 122, 125, 152, 162, 165, 166, 168, 171, 190
heat-killed uropathogenic 126, 127
resistance pattern of 119
uropathogenic 125, 140
Estrogen deficiency 52
Extended spectrum B lactamases 54, 59, 113, 116
External matrix, formation of 139, 139f
Extracellular polymeric substance 135
Fallopian tubes 10
Febrile episodes 98
Fecal soiling 68
Fever 38, 39, 59, 96
Fine needle aspiration 8
Flank pain 9, 38
Fluconazole 25, 60, 89
Fluorescence in situ hybridization 5, 145, 146f
Fluorescent dye techniques 4
Fluorofamide 150
Fluoroquinolones 42, 69, 71, 115, 116
Foley's catheter 112
Fosfomycin 59, 71, 115, 116, 121
Fungal infections 15, 60, 89
Funguria 27
Fusobacterium anaerobic cocci 163
Gardnerella vaginalis 162
Gastrointestinal tract 112
Genitourinary abnormalities 75, 112
surgery 60
system 15
tract 1, 16, 68
tuberculosis 1, 3, 12
diagnosis 3
etiology 1
investigations 3
pathophysiology 1
treatment 8
Gentamicin 120
Gerota's fascia 39, 186
Glomerulonephritis membrane 170
Glomerulosclerosis 39
Glycocalyx 135
Glycolipids 139
Glycyclins 120
Golf-hole appearance 2
Graft dysfunction 88
Granulomatous diseases 186
Hematuria 38, 195
Hemodialysis 52
Hemolysin 169
Hemorrhage 8
interstitial 39
High blood glucose level 38
Histoplasma capsulatum 16
Huang and Tseng classification 36, 37, 43
Human immunodeficiency virus infection 33
Human leukocyte antigen 160
Hydrogen 34
Hydronephrosis 2, 9, 193f
Hydrophilic catheters, use of 62
Hydroureteronephrosis 186f
Hypertension 11
Imipenem 59, 120
Immunoglobulin G 126
Indwelling urinary catheters 19, 101, 102, 114
Infarction 39
atypical 90
severe 59
Infectious Diseases Society of America 51, 74, 81
Inflammatory cell infiltration, acute 39
Intensive care unit 50, 94, 114, 116
Interferon-gamma release assays 4
Intracellular bacterial communities 125, 140
Iontophoresis 149
Isonicotinic acid hydrazide 9
Kerr's kink 8
Ketoacidosis, diabetic 38
Kidney 1, 8
malakoplakia of 196
nonfunctioning 11
Kidney, ureter and bladder 34, 39, 68, 185f
plain radiograph of 179
radiograph of 180f, 181f
Klebsiella pneumoniae 33, 42, 45, 54, 77, 96, 113, 126, 162, 173
Lactic acid 75
Lactobacillus acidophilus 75
Leukocyte count 38
Levofloxacin 59
Linezolid 59
Liposomes 150
Low energy surface acoustic waves 151
Low estrogen state 75
Macrolides 148
Magnetic resonance 192
imaging 21, 41, 184, 189, 194
diffusion-weighted 41
urography 184
Malakoplakia 195, 196
Matrix-assisted laser desorption 145
Meningitis 115
Menopause 75
Meropenem 59, 120
Metabolic disorders 186
Methenamine salts, use of 62
Michaeli classification 34
cure 112
failure 112
infections 135
Microhematuria 38
Minimum biofilm
eradication concentration 148
inhibitory concentration 148
Minocycline 121
Morganella morganii 54, 77, 126, 173
Moth eaten appearance of calyces 8
Mucorales 27
Mucormycosis 22f
diagnosis of 27
Multidetector computed tomography 183, 184
bacteria, gastrointestinal decolonization of 71
tuberculosis, treatment of 10
Multiplanar reconstruction 183
Multiple cortical cysts 190f
Multiple organ failure 46
Mycobacterial growth indicator tubes 163
avium-intracellulare 1
bovis 1
fortuitum 1
haemophilum 88
kansasii 1
tuberculosis 1, 5, 6, 90, 163, 164
direct test, amplified 5, 6
xenopi 1
Nanoparticles 149
Nausea 38, 120
Nephrectomy 11, 44, 90
delayed 44
emergency 44
laparoscopic 44
Nephrolithiasis 45
Nephropathy, diabetic 33
Nephroscopy 27
Nephrostomy 24, 25, 27
percutaneous 112
Nephrouretrectomy 11
Netilmicin 120
Neutropenia 97
Nitrofurantoin 70, 71
Nitrogen 38
Noncontrast computed tomography, coronal section of 186f, 191
Nosocomial infection 135
Nucleic acid 139
amplification 5
Obstructed transplant ureters, treatment of 90
Oral diarylquinoline 10
Orchitis 88
Organic acids 38
Oxygen 38
Pain, renal 195
Pancreatitis, acute 187
Pandrug resistance 112
Papillary necrosis 8, 195
Pelvicalyceal system 192
Peptide nucleic acid 5
Perinephric tissue 34
Perirenal abscess 187
Periurethral Littré glands 182
Phantom calyx 8
Piperacillin 59
Pipe-stem ureters 2, 8
Planktonic bacteria, reversible attachment of 139f
Platelet count 38
Pneumaturia 32, 38
Pneumocystis jirovecii 33
Pneumonia 115
Polycystic kidney disease 33, 87
Polyglucosamine 139
Polymerase chain reaction 5, 6, 21, 56, 90, 146
Polymyxin 115, 116, 120
Povidone-iodine solution 62
Praziquantel 91
Prednisone, high-dose 10
Prerenal azotemia 33
antibiotic therapy 62
antimicrobials, use of 62
Prostate 2
benign enlargement of 90
transurethral resection of 2
Prostatitis 115, 197
bacterial 51
candidal 19
chronic 197
Proteins 139
Proteinuria, severe 38
mirabilis 33, 42, 54, 57, 77, 106, 107, 141, 152, 162, 171173
vulgaris 126, 141, 173
rettgeri 141, 173
stuartii 77
Proximal hydroureteronephrosis, bilateral 187f
aeruginosa 77, 96, 113, 138, 143, 149, 162, 172, 173
biofilms 137
fluorescens 139
multidrug-resistant 113
Psoas hitch 12
Purified protein derivative tuberculin 3
Purple urine bag syndrome 97
Putty kidney 1
Pyelitis, emphysematous 36
Pyelogram, intravenous 34, 39
intravenous 195
retrograde 7
Pyelonephritis 38, 41, 56, 59, 82, 87, 99, 112, 165, 169, 179, 186, 188f, 192
acute 33, 89, 184, 185, 187
chronic 39, 188, 190f
complicated 79
emphysematous 32, 39, 45, 46, 56, 181f, 190, 191f, 192, 194
simple 79
Pyonephrosis 192, 193f
Pyuria 38, 39, 79, 98
Quinolones 42, 119
Quorum sensing inhibitors 151
Reconstructive surgery 11
abscess 35, 56, 187, 189f
anomaly, congenital 180
cell carcinoma 33
cortical cyst 189f
disease 97
failure 58, 104
function impairment, acute 44
papilla, destruction of 1
parenchyma 34, 36f, 37f, 76, 193f
acute bacterial infection of 32
pelvicalyceal system 185
transplant recipient 88, 90
Roche Amplicor Mycobacterium tuberculosis PCR test 5
Salmonella typhi 164
Salmonellosis 88
Salmonelluria 89
Saprophytic opportunistic fungi 27
Schistosoma haematobium 90
Schistosomiasis 87, 180
Self-start intermittent therapy 71
Sepsis 33, 82
Serratia 68, 162
Shock 38, 44, 46, 50
Spermatic cord 10
Spinal cord injury 75, 76
Split bolus technique 183
Staghorn calculus 179, 194f
aureus 54, 77, 95, 149, 164
epidermidis 151, 162
saprophyticus 162, 173
Sterile pyuria 79, 90, 195
Steroids 10
Streptococcus mutans 137
Stress urinary incontinence 68
Sulfamethoxazole 71
catheterization 62
tubes 112
Tamm-Horsfall protein 76, 159
Tazobactam 59
Testis 2
Tetracyclines 121
Thrombocytopenia 38, 44, 45
Tigecycline 115, 116, 120
Tobramycin 59, 120
Transrectal ultrasonography, high-resolution 7
Trimethoprim 71
Tubercle bacilli, demonstration of 3
Tuberculosis 1, 88, 179, 194
Tuberculous bacilli 4
Tuberculous peptide nucleic acid 5
Tumors 180
Ultrasonography 7, 41, 182, 193
Ureaplasma urealyticum 162
Ureter 2, 8, 10
Ureteral orifice, fibrosis of 2
reimplantation 12
stents 52, 75
stricture 11
Ureteritis 88
tuberculous 2
Ureteroureterostomy 12
catheters 75
contamination 74
length 75, 76
secretions 104
Urethrogram, retrograde 180, 182
Urinary bladder 75, 87
mucormycosis of 222
Urinary calculi, treatment of 90
Urinary catheters 100
early removal of 89
insertion of 103
maintenance of 103
perioperative management of 102
Urinary complicating factors 112
Urinary drainage 90
Urinary fluoroquinolones 59
Urinary incontinence 61, 67
Urinary infections 51, 54
complicated 51
uncomplicated 51
Urinary obstruction 53, 58
acute anatomic 61
functional 61
Urinary retention 52
Urinary tract 77, 100
infection 33, 50, 51, 55, 57, 61, 66, 68, 87, 115, 115t, 134, 159, 162, 179
aspergillus 25
bacterial 18
biofilm in 140
catheter-associated 16, 50, 51, 59, 62, 94, 97t, 100, 101t, 116, 141, 162
fungal 15, 18, 60
healthcare-associated 53, 94
multidrug-resistant 111
nosocomial 54
pathogenesis of 124
prophylaxis of 90
radiology of 179
recurrent 66, 67, 69, 90, 91, 124
risk factors for 52t
severe 53
vaccines for 124
instrumentation of 52
isolated mucormycosis of 27
obstruction 19, 188
Urinary tuberculosis 8t
Urine 74
culture 58
output, rigorous monitoring of 52
routine 80
studies 4
Urogenital surgery, history of 67
Urography, intravenous 5, 7, 8t, 179, 180
Urolithiasis 112
Urologic surgery 53
Uropathogens, adhesion of 125
Urosepsis 59, 89
Urothelial tract 185f
Urothelium, infection of 19
Vaccination strategies 126
Vaginal estrogen 69
replacement 69
Vancomycin 59
resistant enterococci 59
Vascular thrombosis 39
Vesicoureteral reflux 2, 76, 188
Vomiting 38, 120
Wan classification 34, 45
Xanthogranulomatous pyelonephritis 46, 179, 192, 193
Ziehl-Neelsen stain 4
Zuckerkandl fascia 186
Zygomycetes 27
Chapter Notes

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Genitourinary TuberculosisCHAPTER 1

Varun Mittal,
Rajat Arora,
Rakesh Khera
An estimated 4–20% of individuals with pulmonary tuberculosis (TB) develop genitourinary involvement, mostly in developing countries.1,2 In patients with miliary disease, 25–62% have been documented to have concomitant renal lesions.3
The most common pathogen associated with TB is Mycobacterium tuberculosis. Uncommonly implicated pathogens include Mycobacterium kansasii, Mycobacterium fortuitum, Mycobacterium bovis, Mycobacterium avium-intracellulare and Mycobacterium xenopi.
Generally primary infection is in the form of pulmonary TB. Genitourinary tract is believed to be involved secondarily. Clinical symptoms usually develop 10–15 years after the primary insult.
Kidney is usually infected by hematogenous spread of bacilli from a primary focus of infection. Mycobacterial seeding leads to granuloma formation in proximity to glomeruli which may heal with fibrosis or may caseate and rupture into the tubular lumen.4,5 Destruction of renal papilla can lead to calyceal ulceration or abscess formation. Involvement of the collecting system may result in fibrotic scarring and stenosis with calcification and called “putty kidney”.2
Tuberculous ureteritis is always an extension of the disease from the kidney. It often causes ureteral strictures and hydronephrosis. The most common site is the lower third of ureter. Rarely, a pan- ureteric stricture takes the form of corkscrew or pipe stem ureter.
Bladder lesions are without exception secondary to renal TB. The earliest forms of infection start around one or another ureteral orifice. It initially manifests as superficial inflammation with bullous edema and granulation. Fibrosis of the ureteral orifice can lead to stricture formation with hydronephrosis or scarring (i.e. golf-hole appearance) with vesicoureteral reflux.
Severe cases involve the entire bladder wall, where deep layers of muscle are eventually replaced by fibrous tissue, thus producing a thick fibrous bladder with progressive reduction of bladder capacity (thimble bladder).
Prostatic TB is also the result of hematogenous spread, but involvement is rare. In many cases, pathologists diagnose it incidentally after transurethral resection of the prostate (TURP). On digital rectal examination, it feels like a firm granulomatous nodule, and needs to be differentiated from malignancy. Very rarely, in acute fulminating cases, it spreads rapidly and presents as perianal sinus.
Epididymis and Testis
In children, it is hematological spread, while in adults it seems to directly spread from the urinary tract through the retrograde route. The formation of a draining sinus is uncommon in developed countries, but epididymal induration and beading of the vas are common. Involvement of the testis is usually due to direct extension. Infertility may result from bilateral vasal obstruction. Nodular beading of the vas is a characteristic physical finding. Orchitis and the resulting testicular swelling can be difficult to differentiate from other mass lesions of the testes.3
The presentation is often vague, and physicians must have a high degree of awareness to make the diagnosis. Symptoms are generally chronic, intermittent, and nonspecific. The most common symptoms are urinary frequency, urgency, dysuria, suprapubic pain, blood or pus in the urine, and fever. Urinary urgency is unresponsive to all treatment when the bladder is extensively involved. Painless gross and microscopic hematuria occurs in approximately 10% and 5% of cases. Unexplained infertility in both men and women may be attributable to genitourinary tuberculosis (GUTB).
Physical examination is typically unremarkable. Tender testicular or epididymal swelling, nodularity and beading of the spermatic cord and vas may be the most telltale physical signs of GUTB one can find. In late cases, epididymocutaneous sinus formations may develop. Nodularity over the surface of prostate may be felt on digital rectal examination.
The diagnosis of GUTB is established by demonstration of tubercle bacilli in the urine; the constellation of dysuria, sterile pyuria, hematuria, and characteristic radiographic findings are highly suggestive of the diagnosis.6 In the absence of alternative explanation for persistent sterile pyuria, 3–6 urine cultures for acid-fast bacilli (AFB) should be performed (regardless of perceived risk for TB) together with radiography.
Purified Protein Derivative Tuberculin
As many as 88% of persons with GUTB have been documented to have a positive purified protein derivative (PPD);7 one study including 100 women with laparoscopically confirmed infection noted a sensitivity and specificity of 55% and 80%, respectively.84
Interferon-gamma Release Assays
There are few data evaluating the utility of interferon-gamma release assays (IGRAs) for diagnosis of GUTB. In one study including 111 Chinese patients with extrapulmonary disease and 8 with GUTB, the sensitivity and specificity of the T-spot IGRA test was 100% and 67%, respectively.9
Urine Studies
Acid-fast Bacillus Smear
Tuberculous bacilli are shed into the urine intermittently, and AFB smear is often negative since the cutoff for a positive smear is 5,000 organisms per milliliter. Serial early-morning urine collection (at least 3) is a specific (89–96%) but less sensitive (approximately 52%) tool.
Acid-fast Bacillus Urine Cultures
It is still considered the criterion standard for evidence of active disease, with sensitivity of 65% and specificity of 100%. Between 11% and 80% of single urine specimens are positive for AFB culture in patients with active disease, depending on the demographic group and stage of infection.10 Therefore, 3–6 first morning midstream specimens should be obtained for AFB culture to maximize the likelihood of a positive result.
Every effort should be made to process the samples immediately after collection. Sending cultures before starting antitubercular treatment and adjusting therapy according to sensitivity in case of resistance is always recommended. The following culture methods are available:
  • Solid media: The Lowenstein-Jensen medium yields results in more than 4 weeks.
  • Radiometric media: The BACTEC 460 medium yields results in 2–3 days.
Identification of acid-fast organisms in the urine sediment via Ziehl-Neelsen stain or fluorescent dye techniques is not diagnostic for TB, since nonpathogenic mycobacteria may be present. 5False-negative results may occur in the setting of concomitant antituberculous or antibacterial therapy capable of inhibiting mycobacterial growth (particularly fluoroquinolones).
Polymerase Chain Reaction
The polymerase chain reaction (PCR) test has been extensively studied and has been proven highly sensitive, specific, and rapid. In various studies, data show sensitivity ranging from 87% to 100% (usually >90%) and specificity from 92 to 99.8% (usually >95%).11,12 Compare this with cultures (37%), bladder biopsies (47%), and intravenous urography (IVU) examinations (88%). Along with an accurate clinical assessment, PCR is the best tool available for avoiding a treatment delay because results are available in only about 6 hours. The following PCR tests are available with near-equivalent quality:
  • Genus-specific 16S ribosomal ribonucleic acid (rRNA) PCR test
  • Species-specific IS6110 PCR test
  • Roche Amplicor M. tuberculosis PCR test
  • Amplified M. tuberculosis Direct Detection Test (AMDT)
Tuberculous Peptide Nucleic Acid Fluorescence in situ Hybridization
Fluorescence in situ hybridization (FISH) using peptide nucleic acid (PNA) probes allows differentiation between tuberculous and nontuberculous mycobacteria in smears of mycobacterial cultures. PNA molecules are pseudo-peptides with deoxyribonucleic acid (DNA)-binding capacity in which the sugar phosphate backbone of DNA has been replaced by a polyamide backbone.
Nucleic Acid Amplification
Nucleic acid amplification allows both detection and identification of M. tuberculosis through enzymatic amplification of bacterial DNA. The most widely used technique is PCR, but transcription mediated amplification (TMA) and strand displacement amplification (SDA) are also commercially used. The sensitivity of this test is higher than that of smear microscopy but it is slightly lower than that of culture techniques. The main advantage of these tests is that they offer quick results, paired with a high level diagnostic accuracy. 6Some individual laboratories offer validated testing, although, thus far, there is no commercial nucleic acid amplification test approved by the US Food and Drug Administration (FDA) for detection of mycobacterial nucleic acid in urine.
Transcription-Mediated Amplification/ Amplified M. tuberculosis Direct Test
Transcription-mediated amplification can identify the presence of genetic information unique to M. tuberculosis directly from preprocessed clinical specimens. Amplified M. tuberculosis Direct (MTD) test (Gen-Probe, Hologic) detects M. tuberculosis rRNA directly and rapidly, with sensitivity similar to that of culture techniques. The sensitivity of this test is of 96% and its specificity is 100% for M. tuberculosis on specimens that are smear-positive for acid-fast bacilli. One other disadvantage of the technique is that positive results are recorded for both viable and dead bacilli.
GeneXpert M. tuberculosis Direct/RIF Molecular System
It detects DNA sequences specific for M. tuberculosis and rifampicin resistance by polymerase chain reaction. Data on use of the GeneXpert for diagnosis of extrapulmonary TB are limited. One study of 91 urine samples from patients with suspected TB or nontuberculous mycobacteria infections (including five culture positive samples) noted sensitivity and specificity of 100 and 98.6%, respectively.13 It simultaneously detects TB and rifampin drug resistance. It provides accurate results within 2 hours. It has been strongly recommended by World Health Organization (WHO) for use in diagnosis of TB since December 2010. TBXpert Project was launched in 2013 by WHO to provide equipment to 21 countries for rapid detection of TB and rifampin resistance.
Imaging Studies
Chest and spine radiographs may show old or active lesions. However, chest radiographic findings are negative in 50% cases. 7KUB radiographs reveal calcifications in the kidney and ureter in approximately 50% of patients. Calcifications are intraluminal, as opposed to schistosomiasis, which produces intramural calcifications.
Intravenous Urography
It remains the standard diagnostic imaging studies for renal TB and has 88–95% sensitivity. Approximately 10–15% of patients who present with active renal TB will have normal urographic findings.14
The earliest radiographically detectable changes are cavitary lesions that progress to the papilla and invade the collecting system, causing calyceal disruption. Findings of infundibular stenosis and multiple ureteral strictures are highly suggestive of renal TB. Later findings may include calcifications, scarring and stricture formation (Table 1).15
High-resolution transrectal ultrasonography (TRUS) has become a very useful noninvasive technique. TRUS can reveal abnormalities in the seminal vesicles and ejaculatory duct and can help assess the status of the prostate.
Computed Tomography Scan
This imaging test is increasingly being used as the primary modality of investigation in disorders of the genitourinary tract. It is a highly sensitive to detect disease in early stage. It is a useful adjunct to IVP and is helpful in late or advanced disease for assessing the extent of disease.16,17
Advantages over intravenous urography: Depicts the extent of extrarenal spread of infection.
Important Tool Retrograde Pyelography
It is rarely indicated now except in patients with renal failure in whom the kidneys cannot excrete contrast and to evaluate stricture in the upper urinary tract. It also helps for sampling urine from individual kidneys for microbiology.8
Table 1   Intravenous urography findings in urinary tuberculosis.
  • Kidney
  • Distorted calyces
  • Mucosal irregularities
  • Moth eaten appearance of calyces
  • “Pipe-stem” ureters
  • Papillary necrosis
  • Strictures
  • Decreased contrast enhancement
  • Dilated ureters
  •   Phantom calyx
  • Beaded appearance/“Cork screw” ureter
  •   Autonephrectomy
  • Dilated calyx or entire PCS
  • Mucosal irregularity, decreased capacity
  • Kerr's kink
  • “Thimble” bladder
Cystoscopy and Bladder Biopsy
  • Rarely indicated:
    • Assessing the extent of the disease
    • Response to chemotherapy
    • To rule out acute interstitial cystitis.
  • Cystoscopy:
    • Bladder filling under direct vision
    • Under general anesthesia with a muscle relaxant reduces the risk of hemorrhage.
  • Biopsy:
    • Only to rule out malignancy
    • Not prior to initiation of medical Rx.
Fine Needle Aspiration
Fine needle aspiration (FNA) as a minimally invasive technique plays a prime role in the diagnosis of tubercular epididymitis and epididymo-orchitis. AFB may be detected on FNA smears in up to 60% of these patients.
“End TB strategy” was adopted by the World Health Assembly in May 2014. It outlines global impact targets to reduce TB deaths by 90%, to cut new cases by 80% between 2015 and 2030.9
Treatment with standard antituberculous agents for 6 months is generally successful in eradicating active renal infection due to drug-susceptible TB.18 The treatment regimen varies with whether or not the patient has HIV infection or drug-resistant TB. GUTB responds better to a short course of treatment than pulmonary TB because GUTB carries a lower mycobacterial load. Also, isonicotinic acid hydrazide (INH) and rifampin penetrate well into the cavitary lesions associated with GUTB. A high concentration of INH, rifampin, and pyrazinamide are maintained in urine. The primary aims of treatment are to preserve renal parenchyma and function, to make the patient noninfectious, and to manage comorbid conditions. Urine sterilization generally occurs within 2 weeks of initiating therapy.
In one study including seven patients with culture-confirmed urinary tract disease treated with standard therapy, no relapse was observed.19 Relapse rates among patients who require nephrectomy appear to be relatively low; one large study noted a relapse rate <1%; however, one study of 174 cases in Turkey demonstrated a relapse rate of 19% even after 12 months of therapy.20
Among 135 patients treated for renal TB in the 1960s with 6 months of isoniazid, streptomycin, and para-aminosalicylic acid, 97% had negative follow-up urine culture after 10 years of follow- up; 60–90% of patients required a combination of surgical and medical therapy.21 In a follow-up study of 135 patients with renal TB, who were treated with isoniazid, rifampin, and ethambutol for 6–9 months (1970–1974) or isoniazid, rifampin, and pyrazinamide for 6 months (1975–1977), the cure rate was 100% (measured by urine sterilization); relapse occurred in one patient.
Patients on antituberculous therapy should be monitored for signs and symptoms of upper urinary tract obstruction (i.e. flank pain, renal colic, hydronephrosis) during treatment.22 Clinical worsening may be observed in the first few weeks of antituberculous therapy due to inflammation, followed by fibrosis and obstruction of the collecting system. Ureteral strictures may progress during treatment due to scarring and subsequent narrowing of the lumen. In one retrospective study including 21 kidneys in which ureteral 10strictures developed during the course of antituberculous therapy, 76% developed within the initial 2 months of treatment.22 Early endourologic decompression with ureteral stent or percutaneous nephrostomy placement was associated with lower nephrectomy rate compared with treatment with medication alone (27% vs 66 %). Apart from endourologic decompression, other surgical intervention for GUTB should be delayed until the patient has received at least 4 weeks of antituberculosis medical therapy.22
In patients who are HIV-positive, continue treatment for a total of 9 months to 1 year.
Steroids are indicated for:
  • Severe bladder symptoms
  • Tubular structure involvement (e.g. ureter, fallopian tubes and spermatic cord)
High-dose prednisone (i.e. at least 20 mg thrice daily) for 4–6 weeks is recommended because rifampicin reduces effectiveness and bioavailability of prednisone by 66%.
Bedaquiline (TMC207) is an oral diarylquinoline. It is a novel drug developed specifically for the treatment of TB after more than 40 years since Rifampicin. It was approved by the FDA for the treatment of multidrug-resistant TB in 2012. Bedaquiline binds to adenosine triphosphate (ATP) synthase and interferes with the mycobacterial conversion of adenosine diphosphate into ATP. The recommended dose of bedaquiline is 400 mg daily for 2 weeks, then 200 mg three times per week for the duration of treatment. Bedaquiline has excellent late bactericidal activity, suggesting that it may kill nonreplicating organisms. QT prolongation is observed and therefore caution is advised.23
Delamanid is the second new drug approved for the treatment of multidrug-resistant tuberculosis (MDR-TB). It is a dihydro-nitroimidazooxazole derivative. It acts by inhibiting the synthesis of 11mycobacterial cell wall components, methoxy mycolic acid and ketomycolic acid and is bactericidal in action. QT interval prolongation is a potential side effect.24
Generally, at least 4–6 weeks of chemotherapy with appropriate agents is first tried if immediate surgery is not necessary. In a recent European series, the overall frequency of surgical management in GUTB in the past 20 years was 0.5% of total urological surgical procedures.
Ablative Surgery
  • Indications:
    • Nonfunctioning kidney with or without calcification
    • Extensive disease involving whole kidney, with hypertension, UPJ obstruction
    • Coexisting renal carcinoma.
Partial Nephrectomy
  • Indications:
    • Localized polar lesion containing calcification that has failed to respond after 6 weeks of intensive chemotherapy.
    • An area of calcification that is slowly increasing in size and is threatening to destroy kidney.
  • Indicated for caseating abscess not responding to short course chemotherapy.
Reconstructive Surgery
Ureteric Stricture
Strictures of the lower end of the ureter occur in approximately 9% of patients. If obstruction at the lower end of the ureter is present at the start of chemotherapy, careful observation is required. These strictures may result from edema, and they respond to chemotherapy.12
Endoscopic Management
If there is deterioration or no improvement after a 6-week period, mild strictures in early stages of the disease can be managed by endoscopic means. Balloon dilatation and placement of doubleJ stent can help resolve the obstruction and give permanent relief in a significant proportion of patients.
Surgical Management
Surgical repair of the stricture is carried out if an initial attempt at dilatation has failed. Ureteric reimplantation is usually sufficient for the most common strictures of lower third of ureter. Psoas hitch or Boari flap procedures may be required if the length of ureter is found to fall short for direct ureteroneocystostomy. For the less common strictures of the middle third of the ureter, excision of the stricture and spatulated end-to end ureteroureterostomy is the first choice. Pan ureteral strictures may necessitate an ileal ureter replacement or rarely an autotransplant.
Augmentation Cystoplasty
The treatment of choice for a contracted bladder is augmentation cystoplasty. A vascularized segment of terminal ileum or sigmoid colon is defunctionalized, detubularized, and attached to the bivalved urinary bladder to increase its capacity. For more severe cases with a thimble bladder, augmentation may not be possible and a neobladder or an ileal conduit may be an appropriate choice.
Intravesical instillation of BCG for the treatment of urothelial carcinoma usually causes only a self-limiting, low-grade, superficial cystitis, but cases of disseminated infection have been recorded, and ureteric involvement with ureteric obstruction was observed in 0.3% cases in a large series.25 Renal involvement was found in 0.1% of the 2,602 patients in this series.13
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