Urogenital Infections and Inflammations

T.E. Bjerklund Johansen, F. M.E. Wagenlehner, Y.-H. Cho, T. Matsumoto, J. N. Krieger, D. Shoskes, K. Naber

Medical treatment for urogenital tuberculosis (UGTB)

 Christian Wejse 1

1 Department of Infectious Diseases/Center for Global Health, Dept of Public Health, Aarhus University, Aarhus University Hospital, -, Denmark


Urogenital tuberculosis (UGTB) should in general be treated as pulmonary TB with a four-drug regimen of Isoniazid, Rifampicin, Ethambutol and Pyrazinamide for a total of 6 months, Ethambutol and Pyrazinamide only the first two months. Some patients may need longer treatment (cavitary disease, kidney abscess/malfunction, HIV co-infection). Treatment of multi-drug resistant tuberculosis (MDR-TB) requires use of long-term intravenous treatment with aminoglycosides and other drugs with considerable toxicity for 18–24 months. Complications such as urinary tract obstruction may occur and should be treated with corticosteroids or surgery.

Medical treatment

Treatment of UGTB is in general similar to treatment for pulmonary TB. Treatment according to WHO guidelines with four drugs is used: Isoniazid (INH), Rifampicin (RIF), Ethambutol (ETH) and Pyrazinamide (PYR) as displayed in Table 1 and Table 2. Standard treatment duration is two months of intensive phase with all four drugs daily, followed by 4 or 7 months of continuation phase with only two drugs (INH+RIF), in total 6–9 months. Appropriate treatment with standard antituberculous agents for six months is usually successful in eradicating active UGTB, provided that it is drug-susceptible TB [1], and this is the general recommended duration of treatment [2], [3]. The 4-month continuation phase should therefore be used in the large majority of patients, the 7-month continuation phase should be reserved only for special groups of patients, such as patients with cavitary pulmonary TB with a positive sputum culture after the initial 2-month treatment. TB is often a multiorgan disease, and in case of involvement of CNS or bone/joint, treatment should be prolonged to 12 months. This may also be useful in cases with extensive soft-tissue involvement [4]. In particular patients with major kidney involvement and ab­scess or compromised renal function may need prolonged treatment for 9–12 months. In case of concomitant HIV infection, TB treatment may also be prolonged in particular if the patient is severely immunocompromised, and HIV testing is obligatory prior to any initiation of antituberculous treatment. Some forms of anti-retroviral treatment (ART) for HIV will require modifications in the TB treatment regimen such as replacement of Rifampicin with Rifabutin. In case of concomitant HIV infection, an infectious disease specialist should be consulted for initiation of ART, and combining ART with the necessary TB treatment is a task for a specialist because of several interactions, and this is not outlined here.


Table 1: Treatment regimen for UGTB

Initial 2 months

Isoniazid (INH)

300 mg

Rifampicin* (RIF)

600 mg

Ethambutol (ETH)

1,200 mg

Pyrazinamide (PYR)

2,000 mg

Pyridoxine/B-combin F

20 mg per day or

50 mg every 2nd day

Four-drug combination treatment may be used if available to reduce the pill-burden;
e.g. the widely used Rimstar which contains isoniazid, rifampicin, ethambutol and pyrazinamide.

Weight (kg)





Daily tablets of Rimstar





Continuation phase the following 4 months


300 mg


600 mg


20 mg per day or

50 mg every 2nd day

*Rifampicin should be taken fasting, preferably half an hour before a meal.


Table 2: Dose-reduction according to weight (adults <50 kg)


30–40 kg

40–50 kg


          300 mg

          300 mg


          450 mg

          450 mg


          600 mg

          800 mg


       1,000 mg

       1,500 mg

Treatment of multi-drug resistant tuberculosis

Treatment of multi-drug resistant tuberculosis (MDR-TB) defined as resistance to both RIF and INH is a particular difficult issue, requiring use of toxic and perhaps very expensive drugs. MDR-TB constitutes globally 3.9% of new TB cases and 21% of previously treated cases [5], this equals to 580,000 new cases annually and an estimated 250,000 deaths from MDR-TB [5], unfortunately only 20% of those in need of MDR-TB treatment are enrolled on an MDR-TB treatment program. It is very important that all patients undergoing TB treatment have had samples sent for TB culture prior to treatment in order to be able to do resistance testing.

ln case of multi-drug resistance, the treatment should include the use of at least five drugs assumed to be effective, preferably documented through drug susceptibility tests. Treatment of MDR-TB is very complicated and has a duration of up to two years. In case of drug resistance, an infectious disease specialist with experience in MDR-TB treatment should be consulted, as it is generally kept on few hands because of the considerable toxicity of the drugs. Briefly the main aspects of MDR-TB treatment are outlined here, as MDR-TB constitutes up to 30% of new TB cases and 70% of re-treatment cases in some countries in Eastern Europe [6]. Treatment of MDR-TB may therefore be a very common issue faced in UGTB treatment in some areas. If possible, an expert consilium should be consulted [7]. Globally, only 50% of all MDR-TB cases are successfully treated [5]. If an MDR-TB case is not successfully treated, there is a risk of progression to XDR-TB (extensively drug resistant TB) which means additional resistance to aminoglycosides and fluorquinolones. These patients are even more difficult to treat, hence expert consultations for treatment is obligatory. XDR-TB has been reported in 117 countries and an estimated 9.5% of all patients with MDR-TB have XDR-TB [5].

The main concept in treatment of MDR-TB [8] is to use an injectable agent such as amikacin, kanamycin, or capreomycin (streptomycin is usually not used because of high rates of resistance), a fluoroquinolone (levofloxacin, moxifloxacin or gatifloxacin are recommended), and at least three other agents with probable activity (ethionamide or prothionamide, cycloserine, para-aminosalicylic acid). First line agents (PYR and ETH) with retained activity should also be used. Patients with MDR-TB require a regimen with at least five effective TB medicines during the intensive phase; PYR and four core second-line TB drugs (see Table 3) – one each from Group A and Group B, and at least two from Group C [9], [10].

Table 3: Reduced kidney function (creatinin clearance <30 ml/min); dose-reduction, adults


300 mg x 1 daily (150 mg if clearance <10 ml/min and ÷ dialysis)


600 mg x 1 daily


15–25 mg/kg x 3 per week (avoid if no dialysis)


1,500 mg/(25–30 mg/kg) x 3 per week

In case of haemodialysis: Antituberculous treatment should be given AFTER dialysis

Ideally the injectable agent is administered daily for the first 6–8 months, forming an “intensive phase” of treatment, with the other drugs then continued, forming a “continuation phase” which should last an additional 12–16 months. There is a short course treatment recommended for selected cases, but since extra-pulmonary TB patients are never considered for this, it does not apply to UGTB patients [10]. Very often, adverse effects (nephro- and ototoxicity) will require ceasing treatment with the injectable agent, but it is often possible to manage side effects through dose reduction to 3 times weekly or swapping drugs for remaining alternatives.

In patients with MDR-TB, surgery may also be used as a means to reduce the amount of lung tissue with intractable pathology, to reduce bacterial load and thus improve prognosis [11]. WHO now recommends elective partial lung resection (lobectomy or wedge resection) alongside a recommended MDR-TB regimen [10].

Treatment variations according to species

UGTB is usually caused by Mycobacterium tuberculosis or (in particular in West Africa) by Mycobacterium af­ri­canum. However, Mycobacterium bovis is also part of the Mycobacterium tuberculosis complex and may be seen in UGTB, in particular among elderly patients. Non-tuberculous mycobacteria are rare causes of urinary tract disease, and are not considered here. M. bovis is inherently resistant to PYR. This should therefore be avoided in such cases, and could be replaced with a flouorquinolone.

Renal impairment

In case of renal insufficiency, drug dose adjustments are required for ETH and PYR as these drugs are cleared in the kidneys, INH and RIF can safely be used without dosing adjustments, even in end-stage renal disease. Dose-adjustments are made according to Glomerular Filtration Rate (GFR), as shown in Table 4. For these particular cases, monitoring plasma drug-concentrations is useful if available. PYR may induce hyperuricaemia and hyperuricuria (which may also be used to monitor treatment adherence) but could therefore be harmful in case of urinary tract damages. In such cases, a xanthine oxydase inhibitor (Allopurinol) could be added [12].

Table 4: Drugs used for treatment of multi-drug resistant tuberculosis (MDR-TB)


Name of drug


A. Fluoroquinolones







B. Second-line injectable agents









C. Other core second-line agents









D. Add-on agents

(not part of the core MDR-TB regimen)




High-dose isoniazid











p-aminosalicylic acid










Treatment response

The clinical response to antituberculous treatment is usually excellent because of high urinary concentrations of antituberculous drugs and good renal vascular supply. Sterilization of mycobacteria in urine usually occurs within two weeks after treatment start. Yet, there is often a considerable mortality, just as in TB disease in other organs. This is mostly because of late presentation or co-morbidity, and the overall TB mortality in 2015 was 14.5% [5]. In a UGTB cohort from Thailand the mortality was 26%, with age, comorbidity and no treatment being the major risk factors [13]. In other cohorts, mortality as low as 1% has been reported [14]. Relapse of TB is rare in culture-confirmed urinary tract disease treated with standard therapy [15], even among patients who require nephrectomy [16]. There are also some reports of high relapse rates, up to 20% in Turkey [17], [18], but historical cohorts with long follow-up >10 years indicate that cure rates of close to 100% are generally to be expected on current treatment regimens [19].

Complications during treatment

During antituberculous therapy upper urinary tract obstruction (UTO) may occur [20]. Signs and symptoms of UTO should be monitored (flank pain, renal colic, hydro­nephrosis) in order to detect this debilitating condition, which may occur in the first few weeks of antituberculous therapy. It may be interpreted as a form of paradoxical reaction to treatment, which is often seen in TB, in par­ticular but not only among HIV-infected in combination with initiating antiretroviral therapy [2], [21]. It is caused by inflammation, followed by fibrosis and obstruction of the collecting system [16]. Ureteral strictures may be caused by the disease process prior to treatment, but may also progress during treatment due to scarring and subsequent narrowing of the lumen [3]. Usually, this is occurring within the first two months of treatment [22]. Fibrosis of the bladder wall with reduced capacity is seen in 9% of patients [16]. In severe and neglected cases, bladder contractions may even develop [23].

Treatment of complications

The treatment for obstruction and other manifestations of paradoxical reaction may primarily be surgical and contractions may need major surgical reconstruction [23]. Some reports indicate a very frequent need for surgery, up to 32% of male cases with UGTB in a large India cohort [4]. When urinary tract obstructions occur, anti-tuberculous treatment is not always sufficient, and reconstructive surgery may be indicated [3]. When UGTB has led to major kidney lesions such as caverns, surgical intervention is indicated in advanced cases [24]. All surgical interventions should be performed under the coverage of anti-TB therapy. Adding corticosteroid treatment may be considered in particular in minor strictures, e.g. prednisolon 50 mg daily with gradual rundown over weeks. Supplementary treatment with corticosteroids is not generally recommended in UGTB [2], but there is no reason to fear adding corticosteroids, once the patient is on effective treatment. This will not put the patient at increased risk of disseminated disease and corticosteroid as adjunctive therapy is increasingly used even in pulmonary TB [25].


This chapter was primarily published in the journal GMS Infectious Diseases [26].


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[3] Kulchavenya E, Naber K, Bjerklund Johansen TE. Urogenital Tuberculosis: Classification, Diagnosis, and Treatment. Eur Urol Suppl. 2016 Jul;15(4):112–21. DOI: 10.1016/j.eursup.2016.04.001
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[10] World Health Organization. WHO treatment guidelines for drug-resistant tuberculosis; 2016 update; October 2016 revision. Geneva: World Health Organization; 2016. Available from: http://www.who.int/tb/areas-of-work/drug-resistant-tb/treatment/resources/en/
[11] Fox GJ, Mitnick CD, Benedetti A, Chan ED, Becerra M, Chiang CY, Keshavjee S, Koh WJ, Shiraishi Y, Viiklepp P, Yim JJ, Pasvol G, Robert J, Shim TS, Shin SS, Menzies D; Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB. Surgery as an Adjunctive Treatment for Multidrug-Resistant Tuberculosis: An Individual Patient Data Metaanalysis. Clin Infect Dis. 2016 Apr;62(7):887-95. DOI: 10.1093/cid/ciw002
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The ZB MED – Information Center for Life Sciences, Germany, together with the European Association of Urology (EAU) provided the opportunity to publish a “Living Textbook” on “Urogenital Infections and Inflammations” in an open access form. This “Living Textbook” represents also an update of the Textbook on Urogenital Infections published 2010 by the International Consultation on Urological Infections and the EAU: http://www.icud.info/urogenitalinfections.html.

The “Living Textbook” will cover infections and inflammations of the kidney, the urinary tract, as well as the male and female genital tract considering pathogenesis, diagnostics, treatment, prophylaxis and future aspects. The “Living Textbook” will be structured into about 26 Sections each with two section co-chairs responsible for peer review of the chapters of each section. Each chapter should reflect the background to the topic and highlight all of the critical evidence relating to the subject. The intention is to provide an up to date, concise synthesis of the literature on that topic, and for clinical topics also recommendations based on levels of evidence for contemporary clinical practice, as well as suggested research recommendations.

The editors hope that this “Living Textbook” may become a useful instrument for physicians of different specialties taking care about patients suffering from these diseases.

Truls E. Bjerklund Johansen (Norway),

Florian ME Wagenlehner (Germany),

Yong-Hyun Cho (South Korea),

Tetsuro Matsumoto (Japan),

John N Krieger (USA),

Daniel Shoskes (USA),

Kurt G. Naber (Germany).

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It should be noted that when recommendations are graded, the link between the level of evidence and grade of recommendation is not directly linear. Availability of randomized controlled trials may not necessarily translate into a grade “A” recommendation where there are methodological limitations or disparity in published results.

Alternatively, absence of high level evidence does not necessarily preclude a grade A recommendation, if there is overwhelming clinical experience and consensus. In addition, there may be exceptional situations where corroborating studies cannot be performed, perhaps for ethical or other reasons and in this case unequivocal recommendations are considered helpful for the reader. The quality of the underlying scientific evidence - although a very important factor – has to be balanced against benefits and burdens, values and preferences and costs when a grade is assigned.

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[1] European Association of Urology. Guidelines. Methodology section. 2015 ed. Arnhem: European Association of Urology; 2015. p. 3. ISBN/EAN: 978-90-79754-80-9. Available from: http://uroweb.org/wp-content/uploads/EAU-Extended-Guidelines-2015-Edn..pdf

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Technical University of Munich
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John N. Krieger MD, PhD

University of Washington Section of Urology


Daniel Shoskes MD, PhD

Cleveland Clinic Glickman Urological and Kidney Institute


Yong-Hyun Cho MD, PhD

St. Mary's Hospital, The Catholic University of Korea Department of Urology


Tetsuro Matsumoto MD, PhD

University of Occupational and Environmental Health Department of Urology


Florian M. E. Wagenlehner MD, PhD

Justus-Liebig University of Giessen Clinic of Urology and Andrology


Truls Erik Bjerklund Johansen MD, PhD

Oslo University Hospital Urology Department


Kurt G. Naber MD, PhD

Technical University of Munich


Punit Bansal MD, PhD

R G Stone and Super Specialty Hospital
Department of Urology


Riccardo Bartoletti

University of Pisa
Department of Translational Research and New Technologies


Truls Erik Bjerklund Johansen MD, PhD

Oslo University Hospital
Urology Department


PD Dr. med. Gernot Bonkat

University Basel
alta uro AG, Merian Iselin Klinik, Center of Biomechanics & Calorimetry (COB)


Prof. Tommaso Cai MD

Santa Chiara Regional Hospital
Dept. of Urology


Dr Leyland Chuang

Ng Teng Fong Hospital, National University Health System
Department of Medicine


Prof. Milan Cizman

University Medical Centre
Department of Infectious Diseases


Alison Crawford MSc

Queen's University
Department of Psychology


Pfofessor Svetlana Dubrovina MD, PhD

Rostov Medical State University
Obstetrics and Gynaecology


Dr Valerie Huei Li Gan MBBS (S'pore), MRCS (Edin), MMed (Surg), FAMS (Urology)

Singapore General Hospital
Department of Urology


Philip Hanno

University of Pennsylvania


Ass prof MD Gundela Holmdahl

Queen Silvia Childrens Hospital, Sahlgrens Academy
Pediatric surgery and urology


Udo B. Hoyme

HELIOS Hospital Erfurt Ltd.
Department of Gynecology and Obstetrics


David Hunstad

Washington University School of Medicine
Pediatrics / Molecular Microbiology


Gitte M. Hvistendahl

Aarhus University Hospital


Prof. Michael KOGAN M.D., PhD

Rostov State Medical University
Department of Urology


Dr Akihiro Kanematsu

Hyogo College of Medicine
Department of Urology


Frieder Keller

University Hospital Ulm
Department Internal Medicine 1, Nephrology


Professor Katarzyna Kilis-Pstrusinska PhD, MD

Wroclaw Medical University
Department of Pediatric Nephrology


MD, PhD Tae-Hyoung Kim

Chung-Ang University


John N. Krieger MD, PhD

University of Washington
Section of Urology


Prof Ekaterina Kulchavenya

Novosibirsk Research TB Institute, Novosibirsk State Medical University


Dr Christina Kåbjörn Gustafsson

Ryhov Hospital Jönköping


Dr. Bela Köves

South Pest Teaching Hospital
Department of Urology


Dr. med. Giuseppe Magistro

Ludwig-Maximilians-University of Munich
Department of Urology


Vittorio Magri

Urologic Clinic


András Magyar

South-Pest Hospital
Department of Urology


Professor Emeritus Brian Morris

University of Sydney
School of Medical Sciences


Baerbel Muendner-Hensen

ICA-Deutschland e.V.


Stephen F. Murphy

Feinberg School of Medicine, Northwestern University
Department of Urology


Kurt G. Naber MD, PhD

Technical University of Munich


Prof. Yulia Naboka

Rostov State Medical University
Department of Microbiology


Dr. J. Curtis Nickel MD

Queen's University
Department of Urology


Professor Ralph Peeker MD PhD

University of Gothenburg
Department of Urology


Tamara Perepanova

N.A. Lopatkin Research Institute of Urology and Interventional Radiology


Prof. Gianpaolo Perletti M. Clin. Pharmacol.

University of Insubria
Department of Biotechnology and Life Sciences


Felice Petraglia

Department of Biomedical, Experimental and Clinical Sciences, University of Florence
Obstetrics and Gynecology


Michel Pontari

Temple University School of Medicine
Department of Urology


Dr. Jörgen Quaghebeur PhD. Med. Sci.

University Hospital Antwerp and University Antwerp
Department of Urology


Yazan F. Rawashdeh

Aarhus University Hospital
Paediatric Urology Section, Department of Urology


Professor Claus Riedl MD



Matthew Roberts

The University of Queensland
Faculty of Medicine


PD Dr. med Guido Schmiemann MPH

Institut für Public Health und Pflegeforschung, Universität Bremen
Abteilung Versorgungsforschung


Caroline Schneeberger MD PhD

Academic Medical Center (AMC)


Prof. Dr. med. Peter Schneede

Klinikum Memmingen
Department of Urology


Aaron C. Shoskes

Des Moines University Medical College of Ostheopathic Medicine


Daniel Shoskes MD, PhD

Cleveland Clinic
Glickman Urological and Kidney Institute


Prof. Dr. Roswitha Siener

University of Bonn
University Stone Centre, Department of Urology


Sofia Sjöström

Queen Silvia Childrens Hospital, Sahlgrens Academy
Pediatric surgery and urology


Mathew Sorensen

University of Washington School of Medicine
Department of Urology


Prof. Dr. Dr. Walter Ludwig Strohmaier FEBU

Regiomed-Klinikum Coburg. Medical School Regiomed
Urology and Paediatric Urology


Satoshi Takahashi

Sapporo Medical University School of Medicine
Department of Infection Control and Laboratory Medicine


Professor Paul Anantharajah Tambyah

Yong Loo Lin School of Medicine, National University Hospital
Department of Medicine


Peter Tenke

Jahn Ferenc South Pest Teaching Hospital
Department of Urology


Praveen Thumbikat

Department of Urology


Dr. Jose Tiran Saucedo

IMIGO / Universidad de Monterrey
Obstetrics and Gynaecology


Dominic Tran-Nguyen

Des Moines University


Dean Tripp

Queen's University
Psychology, Anesthesia & Urology



The Catholic University of Korea, St. Vincent's Hospital
Division of Infectious Diseases, Department of Internal Medicine


Florian M. E. Wagenlehner MD, PhD

Justus-Liebig University of Giessen
Clinic of Urology and Andrology


Assoc. Prof. Christian Wejse

Aarhus University, Aarhus University Hospital
Department of Infectious Diseases/Center for Global Health, Dept of Public Health


Prof. Dr. Mete Çek

Trakya University, School of Medicine