Symptomatic management of patients with UTI

Introduction

Symptomatic urinary tract infections (UTIs) are a major public health concern given that UTIs are amongst the most frequent bacterial infections seen in community and healthcare settings, with wideranging severity patterns.¹Wagenlehner FM, Vahlensieck W, Bauer HW, et al. Primary and secondary prevention of urinary tract infections. Urologe A. 2011 Oct;50(10):1248, 1250-2, 1254-6.  ^,2Lane DR, Takhar SS. Diagnosis and management of urinary tract infection and pyelonephritis. Emerg Med Clin North Am. 2011;29(3):539-52. These infections can be stratified into uncomplicated and complicated, and such stratification has proven to be clinically useful.³Wagenlehner FM, Naber KG. Treatment of bacterial urinary tract infections: presence and future. Eur Urol. 2006 Feb;49(2):235-44.   Individuals at increased risk of infection include women, diabetics, the immunocompromised, and those with anatomic abnormalities, impaired mobility, incontinence, advanced age, and instrumentation.⁴Litza JA, Brill JR. Urinary tract infections. Prim Care. 2010 Sep;37(3):491-507, viii.  

Etiology of UTIs

The infectious course in UTIs is determined by bacterial virulence factors on one side and the integrity of host defense mechanisms on the other side. Therefore, depending on virulence determinants of uropathogenic microorganisms and host-specific defense mechanisms, UTI can manifest as cystitis, pyelonephritis (bacterial interstitial nephritis), bacteremia or urosepsis.⁵Hörl WH. Urinary tract infections. Internist (Berl). 2011 Sep;52(9):1026, 1028-31.  

The gram-negative bacillus Escherichia coli (E. coli) is the most predominant pathogen implicated for vast majority of uncomplicated UTIs, and is supposed to cause 80-90% of community-acquired UTIs and 30- 50% of nosocomially-acquired UTIs.⁶Ejrnæs K. Bacterial characteristics of importance for recurrent urinary tract infections caused by Escherichia coli. Dan Med Bull. 2011 Apr;58(4):B4187.   Other causative pathogens include enterococci, Staphylococcus saprophyticus, Klebsiella spp. and Proteus mirabilis.⁷Blondeau JM. Current issues in the management of urinary tract infections: extended-release ciprofloxacin as a novel treatment option. Drugs. 2004;64(6):611-28.  

Prevalence of UTIs

UTIs are a frequent cause of morbidity in both children and adults, and affect up to 10% of children; its recurrence rate is estimated at 30-40%. As such, the incidence in adult males younger than 50 years is low (about 5-8 per year per 10,000); and incidence approaches that of women only in men older than 60 years.⁸Brusch JL, Cunha BA, et al. Urinary Tract Infection in Males. Available at: http://emedicine.medscape.com/article/231574-overview [Accessed on 17/06/2013/].   Thus, women are at greater risk of developing a UTI than men, and UTIs may occur in up to 50% of all women at least once in their lifetimes.⁹Zaffanello M, Malerba G, Cataldi L, et al. Genetic risk for recurrent urinary tract infections in humans: a systematic review. J Biomed Biotechnol. 2010;2010:321082.   In this population, UTIs occur mainly in those without underlying diseases and with no functional or structural anomalies of the urinary tract, consequently most cases in women are considered uncomplicated UTI¹⁰Alós JI. Epidemiology and etiology of urinary tract infections in the community. Antimicrobial susceptibility of the main pathogens and clinical significance of resistance. Enferm Infecc Microbiol Clin. 2005 Dec;23 Suppl 4:3-8.  ; the most common manifestation in women is acute uncomplicated cystitis.¹¹Kladenský J. Urinary tract infections in women–possibilities of differentiated approach in treatment and prevention. Ceska Gynekol. 2012 Feb;77(1):5-9.   Here, mean annual incidence of uncomplicated UTIs is 15% and 10% in those aged 15-39 and 40-79 years, respectively.¹²Mohsin R, Siddiqui KM. Recurrent urinary tract infections in females. JPMA 2010. Available at: http://www.jpma.org.pk/full_article_text.php?article_id=1903 [Accessed on 17/6/2103].]  

Incomplete voiding, elevated intravesical pressure and catheter use consistently contribute to an increased risk of symptomatic UTIs.¹³García Leoni ME, Esclarín De Ruz A. Management of urinary tract infection in patients with spinal cord injuries. Clin Microbiol Infect. 2003 Aug;9(8):780-5.   In hospitals, almost 80% of nosocomial UTIs are associated with urinary catheters, and only 5-10% of urinary infections are caused by invasive manipulations in the urogenital tract.¹⁴Adukauskiene D, Cicinskaite I, Vitkauskiene A, Hospitalacquired urinary tract infections. Medicina (Kaunas). 2006;42(12):957-64.   However, in community, the prevalence of urinary catheterization ranges from 0.02% to 0.07%, and the risk of bacteriuria in patients with urethral catheters is 3%-10% per day.¹⁵Martínez JA, Mensa J. Catheter-related urinary tract infections in the community. Enferm Infecc Microbiol Clin. 2005 Dec;23 Suppl 4:57-66.   In essence, its presence is universal when the device remains in place for 30 days or longer.

Common symptoms in patients with UTIs

Patients with UTIs can present with a variety of signs and symptoms (Box 1).¹⁶Urinary tract infection (UTI). Available at: http://www.mayoclinic.com/health/urinary-tract-infection/DS00286/DSECTION=symptoms [Accessed on 17/6/2013].   Furthermore, each type of UTI may result in more-specific signs and symptoms, depending on which part of urinary tract is infected (Table 1). Here, symptoms for kidney infection (pyelonephritis) typically include high fever and flank pain, as well as urinary symptoms similar to bladder infection (cystitis).¹⁷Treatment of Urinary Tract Infection (UTI). Available at: http://tmedweb.tulane.edu/pharmwiki/doku.php/treatment_of_utis [Accessed on 17/06/2013].  

In addition, symptoms of UTIs may vary dependent on age (Table 2) and gender, and the presence or

absence of a catheter.¹⁸Urinary tract infections and ESBLs. Available at: http://www.docstoc.com/docs/document-preview.aspx?doc_id=87743332 [Accessed on 17/06/2013].  ^,19 Ahmed SM, Swedlund Sk. Evaluation and treatment of urinary tract infections in children. Am Fam Physician. 1998;57(7):1573-1580.   Among young women, symptoms typically include a frequent and intense urge to urinate, and a painful, burning feeling in the bladder or urethra during urination. The amount of urine may be very small. Older women and men are more likely to be tired and weak, and have muscle aches and abdominal pain. Urine may look cloudy, dark, or bloody, or have a foul smell.

In a patient with a catheter, the only symptom may be fever that cannot be attributed to any other cause. Usually, fever is not present if UTIs are in the bladder – fever may mean the infection has reached the kidneys or has penetrated the prostate. Other symptoms of a renal involvement include pain in the back or side below the ribs, nausea, and vomiting.²⁰Urinary tract infections in adults. National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). Available at: http://kidney.niddk.nih.gov/kudiseases/pubs/utiadult/#signs [Accessed on 17/6/2013].  

Findings most useful for identifying infants with a UTI include presence of fever, history of a previous UTI,

and suprapubic tenderness; combinations of findings are more useful than individual findings. In verbal children, abdominal pain, back pain, dysuria, frequency, or both, and new-onset urinary incontinence increase the likelihood of a UTI.²¹Shaikh N, Morone NE, Lopez J, et al. Does this child have a urinary tract infection? JAMA. 2007 26;298(24):2895-904.   Thus, dysfunctional voiding and urge syndrome, per se, significantly increase the risk of developing UTIs in children. Vesicoureteral reflux can increase the risk of pyelonephritis and renal scarring in children with UTIs.²²Shah G, Upadhyay J. Controversies in the diagnosis and management of urinary tract infections in children. Paediatr Drugs. 2005;7(6):339-46.  

Diagnosis of UTIs

Initially, a UTI should be categorized as complicated or uncomplicated (Figure 1).²³Orenstein R, Wong ES. Urinary tract infections in adults. Available at: http://www.aafp.org/afp/1999/0301/p1225.html?printable=afp#afp19990301p1225-t1 [Accessed on 17/6/2013].   While complicated UTI is defined as infection in a patient with structural or functional abnormalities of the genitourinary tract, uncomplicated UTI is infection in a patient without such abnormalities. These abnormalities may include presence of urinary calculi, cystic renal disease, obstruction, anatomic abnormalities, neurologic bladder dysfunction, or a foreign body. In addition, UTIs in patients with transplanted kidneys and metabolic or immunologic illnesses are also considered complicated.²⁴Managing acute uncomplicated cystitis in the era of antibiotic resistance. Available at: http://www.medscape.org/viewarticle/460756 [Accessed on 17/06/2013].   Further categorization of the infection by clinical syndrome and by host (i.e., acute cystitis in young women, acute pyelonephritis, catheter-related infection, infection in men, asymptomatic bacteriuria in the elderly) helps the physician determine appropriate diagnostic and management strategies.

In practice, often the presence of defined signs and symptoms, inferred from history and physical examination, together with a laboratory result (urinalysis), confirms a UTI.²Lane DR, Takhar SS. Diagnosis and management of urinary tract infection and pyelonephritis. Emerg Med Clin North Am. 2011;29(3):539-52.   Patients with uncomplicated UTIs usually present with dysuria, urinary frequency, urinary urgency, and/or suprapubic pain. Fever or costovertebral angle tenderness indicates upper urinary tract involvement. As follows, a diagnosis of uncomplicated UTI can be achieved best by a thorough assessment of patient symptoms with or without the addition of a urine dipstick test.²⁵Mohsin R, Siddiqui KM. Recurrent urinary tract infections in females. J Pak Med Assoc. 2010 Jan;60(1):55-9.   ²⁶Foster RT Sr. Uncomplicated urinary tract infections in women. Obstet Gynecol Clin North Am. 2008 Jun;35(2):235-48, viii.  

Dipstick urinalysis is a widely used diagnostic tool in women 18 to 70 years of age who present with acute dysuria or urgency. A dipstick urinalysis positive for leukocyte esterase and/or nitrites in a midstream

void specimen reinforces clinical diagnosis of UTI. Leukocyte esterase is specific (94-98%) and reliably sensitive (75-96%) for detecting uropathogens equivalent to 100,000 colony forming units (CFU) per mL of urine. Microscopic hematuria may be present in 40 to 60% of patients with UTI.²⁷Mehnert-kay SA. Diagnosis and management of uncomplicated urinary tract infections. Am Fam Physician. 2005;72(3):451-456.  

In general, the predictable nature of the causative bacteria for uncomplicated UTIs makes routine urine cultures not necessary, thus facilitating empiric treatment. However, urinalysis, as mentioned above, may be appropriate for patients who fail initial treatment. While a colony count of 100 CFU per mL has a sensitivity of 95% and a specificity of 85%, the Infectious Diseases Society of America (IDSA) recommends using a colony count of 1,000 CFU per mL (80% sensitivity and 90% specificity) for symptomatic patients. A cut-off of 100,000 CFU per mL defines asymptomatic bacteriuria.²⁷Mehnert-kay SA. Diagnosis and management of uncomplicated urinary tract infections. Am Fam Physician. 2005;72(3):451-456.  

Children aged less than 5 years who have had a febrile UTI require a radiologic evaluation to identify any underlying genitourinary pathology; while older children can undergo a more tailored workup depending on whether there is a febrile UTI or cystitis-type symptoms.²²Shah G, Upadhyay J. Controversies in the diagnosis and management of urinary tract infections in children. Paediatr Drugs. 2005;7(6):339-46.  

Symptomatic management of UTIs

Symptomatic UTI warrants therapy in all patients, and this may in fact be required prior to, or concurrently with, definite antimicrobial treatment needed for clearance of infection.¹³García Leoni ME, Esclarín De Ruz A. Management of urinary tract infection in patients with spinal cord injuries. Clin Microbiol Infect. 2003 Aug;9(8):780-5.   Treatment is generally started before the culture results are available, and subsequently changed to definite culture-specific antimicrobial therapy.

Burning micturition: a major symptom in UTIs

Dysuria is used to describe painful urination, often described by the patient as burning, stinging, or itching. This symptom of burning micturition is particularly important as relating to the clinical presentation in UTIs, and may be present in as many as 93.3% of patients with selected urinary infections.²⁸Agrawal SK, Reddy BS, Bhalla P, Kaur H. Utility of Direct Fluorescent Antibody Test for detection of Chlamydia trachomatis and its detection in male patients with non gonococcal urethritis in New Delhi. Indian J Dermatol Venereol Leprol. 2003;69:144-7.  ^,29Tchoudomirova K, Nuhor PL, Tchapanova A. Prevalence, epidemiological and clinical correlates of genital Chlamydia trachomatis infection. J Euro Acad Dermatol Venereal. 1998; 11 : 214-220.  

A study by Mishra et al³⁰Mishra B, Srivastava S, Singh K, et al. Symptom-based diagnosis of urinary tract infection in women: are we overprescribing antibiotics? Int J Clin Pract. 2012;66(5):493-8.  , designed to determine the diagnostic accuracy of urinary tract symptoms for early identification of UTI in women (n=276) when culture results were not available, found that UTI was prevalent in 46.01% amongst the symptomatic women. Of note, symptoms of urgency, burning sensation during micturition, dysuria, and pyuria were significantly associated with culture positivity. Furthermore, while an absence of pyuria emerged as the best predictor for ruling out UTI even if the woman had symptoms, the combination of urgency, burning during micturition and pyuria was the best predictor of UTI in the study.

Similarly, a recent prospective, observational study, which involved 139 females aged ≥15 years clinically suspected for UTI, found overall prevalence of UTIs to be 45.32%. Again, the most common

urinary symptom presented was burning micturition (73.4%) followed by frequency (43.9%), urgency (20.9%), painful voiding (20.1%), difficulty (5.0%), and nocturnal incontinence (1.4%) (Figure 2).³¹Iram Shaifali, Uma Gupta, Syed Esam Mahmood, Jawed Ahmed. Antibiotic Susceptibility Patterns of Urinary Pathogens in Female Outpatients. N Am J Med Sci. 2012; 4(4): 163-169.   The most common organisms isolated were E. coli (33.1%) and Klebsiella pneumoniae (7.9%), for which the most effective antibiotic was nitrofurantoin.

Potassium citrate in managing painful/burning micturition

Studies have shown that oral potassium citrate effectively increases urinary pH.³²Sakhaee K, Nicar M, HillK, Pak CYC. Contrasting effects of potassium citrate and sodium citrate therapies on urinary chemistries and crystallization of stone-forming salts. Kidney International 1983;24:348-352.   It, thus, results in less acidic urine, achieving its goal of urine alkalinization³³McNally MA, Pyzik PL, Rubenstein JE, et al. Empiric Use of Potassium Citrate Reduces Kidney-Stone Incidence With the Ketogenic Diet. Pediatrics 2009;124(2):e300-4.  , which may cater to the troublesome condition of painful and burning micturition in patients with UTIs.

In fact, in a study in children with two or more episodes of UTI, a normal urinary tract, and with hypercalciuria, treatment with potassium citrate resulted in no further episodes of UTI once normocalciuria was achieved.³⁴López MM, Castillo LA, Chávez JB, Ramones C. Hypercalciuria and recurrent urinary tract infection in Venezuelan children. Pediatr Nephrol. 1999;13(5):433-7.   Moreover, a recent study by Liern et al³⁵Liern M, Bohorquez M, Vallejo G. Treatment of idiopathic hypercalciuria and its impact on associated diseases. Arch Argent Pediatr. 2013;111(2).   noted that sequential therapy, with a normal protein and low sodium diet, potassium citrate and hydrochlorothiazide, reduced hypercalciuria and the incidence of associated diseases, i.e., UTIs, kidney stones, hematuria, and osteopenia.

Potassium citrate versus sodium alkalizers

Potassium citrate, sodium citrate and sodium bicarbonate have been used in urine alkalization since very long. They are metabolized, after absorption, to bicarbonates which are excreted in the urine, thus effectively raising the urinary pH. They are therefore given to relieve discomfort in UTIs, and to prevent the development of uric-acid renal calculi during uricosuric therapy.³⁶Sweetman S. Martindale: The Complete Drug Reference. Edition 37; London: pharmaceutical press; 2011.  

Historically sodium bicarbonate was the first alkalizing agent, which neutralizes gastric acid along with the production of carbon dioxide. This may lead to disturbance in digestion as well as undesirable gaseous side effects.³⁷ Biyani CS, Cartledge JJ. Cystinuria—Diagnosis and Management. EAU-EBU updateseries 4(2006):175-183.  

In addition, sodium-containing salts, such as sodium bicarbonate or sodium citrate (Table 3), should be given extremely cautiously to patients with hypertension, heart failure, edema, renal impairment, eclampsia, or hyperaldosteronism, as they may cause excessive sodium load.³⁶Sweetman S. Martindale: The Complete Drug Reference. Edition 37; London: pharmaceutical press; 2011.  

Further, sodium salts are to be used with caution in patients with low urinary output or reduced glomerular filtration rate (GFR) who are prone to elcectrolyte (K+) and acid-base imbalance. Sodium salts may actually increase cystine secretion.

Citrate forms soluble complexes with calcium, thereby reducing urinary saturation of stone-forming calcium salts. Potassium citrate has a hypocalciuric effect when given orally, probably due to enhanced calcium renal absorption. Urinary calcium excretion is unaffected by sodium citrate since the alkali mediated hypocalciuric effect is offset by a sodiumlinked calciuresis.³⁶Sweetman S. Martindale: The Complete Drug Reference. Edition 37; London: pharmaceutical press; 2011.   As such, studies using sodium bicarbonate administration reveal little effect on urinary calcium excretion, in contrast to studies that used potassium citrate supplementation and found significant reductions.³⁸Minich DM. Acid-alkaline balance: role in chronic disease and detoxification. Alternative therapies 2007;13(4):62-65.  

Potassium citrate is highly beneficial as it is highly palatable, has pleasant taste, and is tolerable even with long term use. It does not neutralize gastric juice or disturbs digestion. Potassium citrate has superior efficacy in urine alkalization for the management of nephrolithiasis, cystinuria, renal tubular acidosis, hypomagnesuria, hypocitraturia, UTI, and in clearing the residual stone fragments after surgical intervention when compared to sodium salts. Various recent studies support the evidence in favour of potassium citrate as the first line urine-alkalizing agent.

Symptom burden of suprapubic pain, urgency, and frequency

Symptoms of UTIs frequently include some combination of dysuria, frequency, urgency, hematuria, and suprapubic pain³⁹Powers RD. New directions in the diagnosis and therapy of urinary tract infections. Am J Obstet Gynecol. 1991 May;164(5 Pt 2):1387-9.   ⁴⁰Stamm WE. Protocol for diagnosis of urinary tract infection: reconsidering the criterion for significant bacteriuria. Urology. 1988 Aug;32(2 Suppl):6-12.  , as well as a recent onset of nocturia⁴¹Tuxford AF. The relationship of urinary symptoms to significant bacteriuria. J R Coll Gen Pract. 1975 Jun;25(155):456-61.  ; all of which needs to be considered for optimal patient outcomes. These functional symptoms of UTIs may have varied presentations, and may manifest in unison. Addition of anti-cholinergic drugs may be considered for these bothersome lower urinary tract symptoms in absence of significant post-void residual urine volumes. However, the concerns that these drugs may predispose to urinary retention, are associated with anti-cholinergic side effects, and may cause drug-drug interactions (as elderly are on polytherapy), warrants their cautious use in carefully selected patients. Men on this therapy who are reporting increased hesitancy or showing signs of increasing post-void residual urine or clinical evidence of retention should be warned to stop the anti-cholinergic element of the combination therapy immediately.

Flavoxate – a preferred anti-spasmodic

In such a setting (see above), the anti-spasmodic flavoxate, free from concerns associated with the use of anti-cholinergics, can be an obvious choice to alleviate this symptomatic burden of UTIs. Flavoxate is a smooth muscle relaxant with wide range of indications that is widely used to treat urgency and urge incontinence. The evidence was presented in a double blind, placebo-controlled trial of flavoxate (600 mg daily), carried out in patients (n=60) suffering from painful conditions of the lower urinary tract arising from inflammation and/or infection or from spasm following diagnostic or therapeutic procedures. Statistically significant improvement was noted in frequency and suprapubic pain, and marked relief was afforded in dysuria, hesitancy and burning.⁴²Baert L. Controlled double-blind trail of flavoxate in painful conditions of the lower urinary tract. Curr Med Res Opin. 1974- 1975;2(10):631-5.  

Similarly, Gu and colleagues⁴³Gu FL, Reng ZY, Shang GZ, et al. Treatment of urgency and urge incontinence with flavoxate in the People’s Republic of China. J Int Med Res. 1987;15(5):312-8.   assessed the effect of giving flavoxate 200 mg thrice daily orally, for two weeks, on 361 patients with urgency/incontinence of various types. Of the 336 patients, 228 (67%) patients were completely cured of urgency/incontinence symptoms, and 66 (20%) were improved. Of note, flavoxate appeared to be quite effective in 77.4% of patients refractory to previous anti-cholinergic treatment. Importantly, treatment did not increase the end-residual volume.

A comparative evidence favouring flavoxate was presented by Gould⁴⁴Gould S. Urinary tract disorders. Clinical comparison of flavoxate and phenazopyridine. Urology 1975;5(5):612-5.  , wherein the author initiated a systematic review to compare flavoxate and phenazopyridine, and evaluated nine trials in which patients with symptoms of UTIs were randomly assigned to treatment with either of the two drugs. Most symptoms improved in more patients on flavoxate therapy than on phenazopyridine therapy. In patients having symptoms of either prostatitis, acute cystitis, urethritis, and/or trigonitis, symptom severity evaluations at 2 and 5 days of therapy showed most symptoms improved in patients on flavoxate therapy than on phenazopyridine therapy. Also, more adverse effects were reported in patients treated with phenazopyridine.

Nitrofurantoin as empirical therapy in the management of UTIs

Antibiotic therapy is required to clear the infectious process from the urinary tract. In this context, high resistance to broad-spectrum antibiotics, especially to extended-spectrum β-lactams, carbapenems, and fluoroquinolones, among uropathogens has emerged as a critical problem in many countries. As follows, attributable to this rising concern of antibiotic resistance, several first-line agents have been recommended for the treatment of acute uncomplicated cystitis. New evidence supports the use of nitrofurantoin as first-line therapy.⁴⁵Colgan R, Williams M. Diagnosis and treatment of acute uncomplicated cystitis. Am Fam Physician 2011;84(7):771-76.   Nitrofurantoin is a good choice for initial empiric therapy of uncomplicated cystitis as it exerts antibacterial activity in the urine, but has little systemic antibacterial effect, and bacterial resistance is uncommon.¹⁷Treatment of Urinary Tract Infection (UTI). Available at: http://tmedweb.tulane.edu/pharmwiki/doku.php/treatment_of_utis [Accessed on 17/06/2013].  

Prophylaxis for recurrent infection

As discussed earlier, symptoms may identify patients with uncomplicated UTIs, thus facilitating definite treatments both directed against the causative pathogen and the bothersome symptoms. Nonetheless, the fact that even urine of healthy women is not sterile⁴⁶Naboka IuL, Kogan MI, Vasil’eva LI, Gudima IA, Miroshnichenko EA, Ibishev KhS. Bacterial mixed infection in women with chronic recurrent cystitis. Zh Mikrobiol Epidemiol Immunobiol. 2011 Jan-Feb;(1):8-12.   suggests considering prophylactic therapy. The study by Alexiou and colleagues appears to solidify the concept.⁴⁷Alexiou Z, Mouktaroudi M, Koratzanis G, et al. The significance of compliance for the success of antimicrobial prophylaxis in recurrent lower urinary tract infections: the Greek experience. Int J Antimicrob Agents 2007;30(1):40-3.   The authors assessed 181 records for lower urinary tract

infections, and found that all 181 women had more than three episodes of cystitis per year; 129 were under continuous prophylaxis, and 52 were under postcoital prophylaxis. Among women treated for ≥6 months, the most effective regimen was nitrofurantoin, with a success rate of 96.8% compared with 82.8% for trimethoprim-sulfamethoxazole (TMPSMX) and 72.3% for norfloxacin (Figure 3).

The efficiency of nitrofurantoin and trimethoprim prophylaxis in preventing recurrent UTIs was compared in a randomized, double blind study in 130 children aged 1 to 14 years (mean 7.5 years).⁴⁸Brendstrup L, Hjelt K, Petersen KE, et al. Nitrofurantoin versus trimethoprim prophylaxis in recurrent urinary tract infection in children. A randomized, double-blind study. Acta Paediatr Scand. 1990;79(12):1225-34.   Children received antibiotics for 6 months. Nitrofurantoin proved to be the most efficient prophylactic drug in patients with abnormal urography and/or reflux as evaluated by actuarial percentage recurrence-free analysis. Nitrofurantoin prophylaxis altered neither the pattern of resistance nor the bacteriological constellation, while patients receiving trimethoprim prophylaxis had 76% trimethoprim resistant bacteria during prophylaxis, compared with 8% before and 17% after prophylaxis. The percentage of recurrences due to E. coli (70-80%) was unaffected by trimethoprim prophylaxis, but the proportion due to trimethoprim resistant E. coli was significantly higher during prophylaxis (65%) than before (6%) and after (11%). The percentage of Staphylococcus epidermidis UTI was significantly higher during trimethoprim prophylaxis (27%) than before (2%). In conclusion, nitrofurantoin was recommended as the first choice prophylactic treatment for children with recurrent UTI and urinary tract abnormalities.

Lifestyle measures

Further to direct therapeutic strategies meant for symptomatic management of UTIs, simple lifestyle modifying measures may also help to alleviate the pain and discomfort of UTIs.¹⁶Urinary tract infection (UTI). Available at: http://www.mayoclinic.com/health/urinary-tract-infection/DS00286/DSECTION=symptoms [Accessed on 17/6/2013].  
These include:

• Drinking plenty of water to dilute urine and help flush out bacteria.
• Avoiding drinks that may irritate the bladder and tend to aggravate urinary urgency and/or frequency. Therefore, avoid coffee, alcohol, and soft drinks containing citrus juices and caffeine, until infection has cleared.
• Applying a warm, but not hot, heating pad to the abdomen to minimize bladder pressure or discomfort.

Conclusion

UTIs continue to be a common clinical problem in both the community and healthcare associated settings, having enormous impact in terms of cost and healthcare resources utilization. The goals of pharmacotherapy are to provide symptomatic relief to patients, to eradicate the infection, and prevent complications. While on one hand, potassium citrate makes the urine less acidic, thereby managing painful and burning micturition, alternatively, flavoxate, a smooth muscle relaxant, is widely used to treat urgency and urge incontinence, and several other symptoms of UTIs, such as frequency, suprapubic pain, dysuria, hesitancy and burning. In addition, given the current prevalence of antibiotic resistance among community uropathogens, nitrofurantoin appears a treatment of choice for most patients with UTIs for clearing the underlying infection.

References

1. Wagenlehner FM, Vahlensieck W, Bauer HW, et al. Primary and secondary prevention of urinary tract infections. Urologe A. 2011 Oct;50(10):1248, 1250-2, 1254-6.
2. Lane DR, Takhar SS. Diagnosis and management of urinary tract infection and pyelonephritis. Emerg Med Clin North Am. 2011;29(3):539-52.
3. Wagenlehner FM, Naber KG. Treatment of bacterial urinary tract infections: presence and future. Eur Urol. 2006 Feb;49(2):235-44.
4. Litza JA, Brill JR. Urinary tract infections. Prim Care. 2010 Sep;37(3):491-507, viii.
5. Hörl WH. Urinary tract infections. Internist (Berl). 2011 Sep;52(9):1026, 1028-31.
6. Ejrnæs K. Bacterial characteristics of importance for recurrent urinary tract infections caused by Escherichia coli. Dan Med Bull. 2011 Apr;58(4):B4187.
7. Blondeau JM. Current issues in the management of urinary tract infections: extended-release ciprofloxacin as a novel treatment option. Drugs. 2004;64(6):611-28.
8. Brusch JL, Cunha BA, et al. Urinary Tract Infection in Males. Available at: http://emedicine.medscape.com/article/231574-overview [Accessed on 17/06/2013/].
9. Zaffanello M, Malerba G, Cataldi L, et al. Genetic risk for recurrent urinary tract infections in humans: a systematic review. J Biomed Biotechnol. 2010;2010:321082.
10. Alós JI. Epidemiology and etiology of urinary tract infections in the community. Antimicrobial susceptibility of the main pathogens and clinical significance of resistance. Enferm Infecc Microbiol Clin. 2005 Dec;23 Suppl 4:3-8.
11. Kladenský J. Urinary tract infections in women–possibilities of differentiated approach in treatment and prevention. Ceska Gynekol. 2012 Feb;77(1):5-9.
12. Mohsin R, Siddiqui KM. Recurrent urinary tract infections in females. JPMA 2010. Available at: http://www.jpma.org.pk/full_article_text.php?article_id=1903 [Accessed on 17/6/2103].]
13. García Leoni ME, Esclarín De Ruz A. Management of urinary tract infection in patients with spinal cord injuries. Clin Microbiol Infect. 2003 Aug;9(8):780-5.
14. Adukauskiene D, Cicinskaite I, Vitkauskiene A, Hospitalacquired urinary tract infections. Medicina (Kaunas). 2006;42(12):957-64.
15. Martínez JA, Mensa J. Catheter-related urinary tract infections in the community. Enferm Infecc Microbiol Clin. 2005 Dec;23 Suppl 4:57-66.
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19. Ahmed SM, Swedlund Sk. Evaluation and treatment of urinary tract infections in children. Am Fam Physician. 1998;57(7):1573-1580.
20. Urinary tract infections in adults. National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). Available at: http://kidney.niddk.nih.gov/kudiseases/pubs/utiadult/#signs [Accessed on 17/6/2013].
21. Shaikh N, Morone NE, Lopez J, et al. Does this child have a urinary tract infection? JAMA. 2007 26;298(24):2895-904.
22. Shah G, Upadhyay J. Controversies in the diagnosis and management of urinary tract infections in children. Paediatr Drugs. 2005;7(6):339-46.
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