Urinary and male genital tract infections-Standard Treatment Guidelines

Infections of the urinary tract pose a serious health problem, also because of their frequent occurrence.

Clinical and experimental evidence support that the ascent of micro-organisms within the urethra is the most commom pathway leading to urinary tract infections, especially for organisms of enteric origin (I.e Escherichia coli and other Enterobacteriaeae). This is a logical explanation for the greater frequency of UTIs in women than in men and the increased risk of infection following bladder catherisation or instrumentation.

Ministry of Health and Family Welfare, Government of India has issued the Standard Treatment Guidelines for Urinary and male genital tract infections.
Following are the major recommendations :

Classification of Urinary and Male Genital Tract Infections

For practical clinical reasons, urinary tract infections (UTIs) and male genital tract infections are classified according to entities with predominating clinical symptoms: (I) uncomplicated lower UTI (cystitis); (2) uncomplicated pyelonephritis; (3) complicated UTI with or without pyelonephritis; (4) Urosepsis; (5) urethritis; and (6) prostatitis, epididymitis, orchitis.

Definitions

the definitions of bacteriuria and pyuria are as follows: Significant bacteriuria in adults:

• > 10³ uropathogens/ml of midstream urine in acute uncomplicated cysitis in female;


• > 10⁴ uropathogens/ml of midstream urine in acute uncomplicated pyelonephritis in female;


• > 10⁴ uropathogens/ml of midstream urine of women or 10⁴ uropathogens/ml of midstream urine in men (or in catheter, urine specimen in women) with complicated UTI.

In a suprapubic bladder puncture specimen any count of bacteria is relevant.

Asymptomatic bacteriuria (ABU)

ABU is defined as two positive urine cultures taken more that 24h apart with 10⁵ uropathogens/ml of the same bacterial strain.

Pyuria

The requirement for pyuria is 10 white blood cells per high power field in the resuspended sediment of a centrifuged aliquot of urine or per mm³ in unspun urine. For the routine, a dipstick method can also be used, including leukocyte esterase test, or nitrite reaction.

Table 1. Classification of prostatitis according to NIDDK/NIH

I	Acute bacterial prostatitis (ABP)
II	Chronic bacterial prostatitis (CBP)
III	Chronic pelvic pain syndrome (CPPS)
	A Inflammatory CPPS: WBC in EPS/voided bladder urine-3 (VB3) or semen
	B Noninflammatory CPPS: no WBC/EPS/VB3/semen
IV	Asymptomatic inflammatory prostatitis

Diagnosis
Disease history, physical examination and urine analysis by dipstick including white and red blood cells as well as nitrate reaction is recommended for routine diagnosis.

In case of suspicion of pyelonephritis, evaluation of the upper urinary tract may be necessary to rule out upper urinary tract obstruction or stone disease.

Diagnosis	Most Frequent pathogens	Initial, empiric antimicrobial therapy	Therapy duration
Cystitis, acute, Uncomplicated	E.coli Klebsiella Proteus Staphylococcus	Trimethoprim/ sulfamethoxazole Fluroquinolonea Alternatives: Fosfomycin Nitrofurantoin	3 days 3 days 1 day 7 days
Pyelonephritis, acute, uncomplicated	E.coli Proteus Klebsiella Other Enterobacteria Staphylococcus	Fluroquinolone Cephalosporin Gr. 2b/3a Alternatives Aminopenicillin / BLI Aminoglycoside	7-10 days
UTI with complicating	E.coli	Fluoroquinolone	3-5 days after defervescence or control/ examination of complicating factor
Factors Nosocomial UTI Pyelonephritis, acute, Complicated	Enterococcus Staphylococcus Klebsiella Proteus Enterobacter	Aminopenicillin / BLI Celphalosporin Gr. 2 Celphosporin Gr. 3 a Aminoglycosides In case of failure of initial therapy within 1-3 days or in clinically severe cases:
	Other Enterobacteria Pseudomonas (Candida)	Anti-Pseudomonas active: Fluroquinolone, if not used initially Acylaminopenicillin/BLI Cephalosporin Gr. 3B Carbapenem + Aminoglycoside In case of Candida Fluconazole Amphotericin B
Prostatitis, acute, chronic	E.coli	Fluroquinolonea	Acute : 2 weeks
Epididymitis,acute	Other Enterobacteria	Alternative in acute bacterial prostatitis
	Pseudomonas	Cephalosporin Gr. 2	Chronic : 4-6 weeks or longer
	Enterococcus	Cephalosporin Gr. 3a/b
	Staphylococcus	In case of Chlamydia or Ureaplasma:
	Chlamydia	Doxycyline
	Ureaplasma	Macrolide
Urosepsis	E.coli	Cephalosporin Gr. 3a/b	3-5 days after defervescence or control/ elimination of complicating factor
	Other Enterobacteria	Fluorquinolonea
	After urological interventions -	Anti-Pseudomonas active Acylaminopenicillin/BLI
	pathogens: Proteus Serratia	Carbapenem Aminoglycosides
	Enterobacter Pseudomonas

a Fluroquinolone with mainly renal excretion; BLI= B- lactamase inhibitor. B 1 st,2nd and 3rd generation respectively (3a - without; 3b - with anti-Pseudomonas activity)

Treatment

Treatment of UTI is dependent on a variety of factors. An overview of most frequent pathogens, antimicrobial agents and duration of treatment in various conditions is given in table 2. Patients with recurrent UTI may be recommended prophylactic treatment. The following regimens have a documented effect in preventing recurrent UTI in women (table 3).

Agent	Dose
Standard regimens (taken at bedtime) Trimethoprim / sulfamethoxazole Trimethoprim	40/200mg/day or 3 times weekly 100mg/days
Nitrofurantoin Others Cephalexin Norfloxacin	50mg/day 125 or 250 mg/day 200 mg/day
Ciprofloxacin	125 mg/day

Special situations:

• UTI in pregnancy. Asymptomatic bacteriuria is treated with a 7 day course based on sensitivity testing. For recurrent symptomatic infections, either cephalexin 125-250 mg/day or nitrofurantoin 50 mg/day may be used.


• UTI in postmenopausal women. In women with recurrent infection intravaginal estriol is recommended. If this does not work, in addition antibiotic prophylaxis is indicated.

• UTI in children. Treatment perioud should be extended to 7-10 days. Tetracyclines and fluroquinolones should not be used due to effects on teeth and cartilage.

• Acute uncomplicated UTI in young men. The treatment should last at least 7 days.

• UTI in diabetes mellitus and renal insufficiency. After treatment, a prophylactic regimen may be recommended afterwards.

• Complicated UTI due to urological disorders. The underlying disorded must be managed if permanent cure is to be expected. In order to avoid inducing resistant strains, treatment should be guided by urine culture whenever possible.

• Sepsis syndrome in Urology (urosepsis).

Patient with UTI may develop sepsis. Early signs of systemic inflammatory response (fever or hypothermia, tachycardia, tachypnea, hypotension,oliguria, leukopenia) should be recognized as the first signs of possible multiorgan failure. In conjunction with appropriate antibiotic therapy, life supporting therapy in collaboration with an intensive care specialist may be necessary. Any obstruction in the urinary tract needs to be drained.

Follow-up of patients with UTI

for follow-up after uncomplicated UTI and pyelonephritis in women, a urinanalysis by dipstick is enough for routine use.

In women who will have recurrence within 2 weeks, repeated urinary culture with antimicrobial testing and evaluation of the urinary tract is recommended.

In the elderly, newly developed recurrent UTI may warrant a full evaluation of the urinary tract.

In men with UTI, a urologic evaluation should be done when the patient is in adolescence, in cases with recurrent infection and in all causes with pyelonephritis. Also patients with prostatitis, epididymitis and orchitis should follow these recommendations.

In children, investigations are indicated after two episodes of UTI in girls and one episode in boys. Recommended investigations are ultrasonography of the urinary tract supplemented by voiding cystourethrography.

Urethritis

Symptomatic urethritis is characterized by dysuria and purulent discharge

Diagnosis

The Gram stain of secretion or urethral smear showing more than 5 leukocytes per high power field (HPF) (1,000) and eventually gonococci located intracellularly as Gram-negative diplococci indicate a pyogenic urethritis. A positive leukocyte esterase test or more than 10 leukocytes per high-power field (400) in the first voiding urine specimen are diagnostic.

Therapy

The following guidelines for therapy comply with the recommendations of the Centre for Disease Control and Prevention (1998).

For the treatment of gonorrhea the following antimicrobials can be recommended:

Cefixime 400 mg orally As a single dose Cefriaxone 250 mg i.m. As a single dose (i.m. with local anaesthetic)

Ciprofloxacin 500 mg orally as a single dose Ofloxacin 400 mg orally as single dose

As gonorrhea is frequently accompanied by chalamydial infection, an antichlamydial active therapy should be added. The following treatment has been successfully applied in C. trachomatis infections :

First choice	Second choice
Azithromycin 1 g (=4 caps.@250 mg) orally as single dose	Erythromycin 500 mg orally 4 times daily for 7 days
Doxycycline 10 mg 2 times daily orally for 7 days	Ofloxacin 200 mg orally for 7 days

if therapy fails, one should consider infections by T. vaginalis and / or Mycoplasma, which can be treated with a combination of metronidazole (2 g orally as single dose) and erythromycin (4 times daily 500 orally for 7 days).

Prostatitis, Epididymitis and Orchitis

Prostatitis

Treatment

• Acute bacterial prostatitis can be a serious infection and parenteral administration of high doses of bactericidal antibiotic such as aminoglycosides and a penicillin derivative or a 3^rd generation cephalosporin are required until defervescence and normalization of infection parameters. In less severe cases a fluoroquinolone may be given orally for at least 10 days.


• In chronic bacterial prostatitis and chronic inflammatory pelvic pain syndrome, a fluoroquinolone or trimethorpim should be given orally for 2 weeks after the initial diagnosis. Then the patient should be reassessed and antibiotics only continued if pretreatment cultures were positive or if the patient reports positive effect of the treatment. A total treatment period of 4-6 weeks is recommended.

Epididymitis, Orchitis

The majority of cases of epididymitis are due to common urinary pathogens. Bladder outlet obstruction and urogenital malformations are risk factors for this type of infection.

Treatment

Prior to antimicrobial therapy a urethral swab and midstream urine should be obtained for microbiological investigation. Fluoroquinolones, preferably those which react well against C. trachomatis (e.g. ofloxacin, levofloxacin) should be first choice drugs because of their broad antibacterial spectra and their.

Table 4. Recommendations for perioperative antibacterial prophylaxis in urology

Procedure	Most common pathogens (s)	Antibiotic(s) of choice	Alternative antibiotic(s)	Remarks
Open operations urinary tract including bowel segments	Enterobacteria Enterococci Anaerobes Wound infection: Staphylococci Enterbacteria Enterococci Wound infection: staphylococci Staphylococci Staphylococci	Aminopenicillin + BLI Cephalosporin 20 + Metronidazole	In high-risk patients: Cephalosporin3 Acylaminopenicillin + BLI	In all patients
Urinary tract without bowel segments		Fluoroquinolone Cephalosporin 20 Aminopenicilin +BLI	in high-risk patients: Cephalosporin3 Acylaminopenicillin + BLI	in patients with increased risk of infection
Implant / prosthesis: penis, sphincter Reconstructive genital operation		Cephalosporin 10 /20 Cephalosporin 10 /20		in all patients in secondary operations & in patients with increased risk of infection
Other interventions outside of the		Cephalosporin 10 /20		in patients with increased risk of infection
urinary tract
Endoscopic – instrumental operations Urethra, prostate, bladder, ureter, kidney, incl. percutaneous litholapaxy and ESWL	Enterobacteria Staphylococci Enterococci	Fluoroquinolone Aminopenicillin + BLI Cephalosporin 20 Fosfomycin Trometamol	Cotrimozazole Aminoglycoside	In patients with increased risk of infection
Diagnostic intervention Transrectal biopsy of the prostate (with thick needle)	Enterobacteria Enterococci Anaerobes Streptococci Enterobacteria Enterococci Staphylococci	Fluoroquinolonea Aminopenicllin + BLI Cephalosorin 20 + Metronidazole Fluoroquinolonea Aminopenicillin + BLI Cephalosporin 20	Aminoglycoside Cotrimozazole	In all patients
Perineal biopsy of the prostate, urethrocystosc opy, ureterorenosco py, percutaneous pyeloscopy, laparoscopic procedures			Cotrimoxazole	In patients with increased risk of infection

BLI = B- Lactamase inhibitor, ESWL- extracorporeal shock-wave lithotripsy. 10 ,20 ,30 = 1st, 2nd, 3rd generation respectively.

11. Fluroquinolone with sufficient renal excretion

Favorable penetration into the tissues of the urogenital tract. In case C. trachomatis has been detected as etiologic agent, treatment could also be continued with doxycycline 200 mg/day for a total treatment period of at least 2 weeks. Macrolides may be alternative agents. In case of C .trachomatis infection, the sexual partner should be treated as well.

Antibiotics and α Blockers in combination

Urodynamic studies have shown increase urethral closing pressure in patients with chronic prostatitis. A combination treatment of α blockers and antibiotics is reported to have a higher cure rate than antibiotics alone in inflammatory CPPS. This is a treatment option favored by many urologists.

In general, surgery should be avoided in the treatment of prostatitis patients except for drainage of prostatic abscesses.

Perioperative Antibacterial Prophylaxis in Urological Surgery

The main aim of antimicrobial prophylaxis in urology is to prevent symptomatic / febrile genitourinary infections, such as acute pyelonephritis, prostatitis, edpididymitis and urosepsis as well as serious wound infections.

Antibiotic prophylaxis is recommended only for a maximum of 24 hours after surgery in most situations. More rampant use leads to antibiotic resistance and places an additional economic burden. Prophylaxis does not substitute for poor surgical asepsis.

Guidelines by The Ministry of Health and Family Welfare :

Prof. Rajesh Ahlawat
Chairman,
Department of Urology & Kidney Transplant,
Medanta Medicity
Reviewed By:
Dr Anup Kumar Gupta
Head of Department
Department of Urology
VMMC and Safdarjang Hospital,
New Delhi