INTRODUCTION: The treatment of rUTI is more complex in the era of increasing antibiotic resistance. After counseling and behavioral modification, guidelines recommend antimicrobial prophylaxis[1]. Use of prophylactic antimicrobial therapy in young healthy patients reduced the number of rUTI in trials conducted in 1970-1990’s, when resistance rates were lower. In this era when there is limited availability of oral antimicrobials due to increasing antimicrobial resistance, availability or side effects , systemic therapy would augment the emergence of resistant organisms, further limiting the antimicrobial treatment options. Particularly in patients with complex urological history, including neurogenic bladder, intermittent catheterization, renal transplant, the pattern of uropathogens and sensitivity differ from general population.

Intravesical instillation of gentamicin may be an alternate treatment option for rUTI in some patients. Aminoglycosides have concentration dependant antimicrobial activity. By direct intravesical instillation higher concentrations at the site of infection can be achieved well above the MIC of the uropathogens. Antimicrobial resistance is unlikely to develop due to high drug concentration. With local use of gentamicin lead to the clearance of MDR organisms. Side effects related with aminoglycosides ( nephrotoxity, ototoxity) are minimal.

Instillation of therapeutic agents into the bladder to combat recurrent urinary tract infections (rUTIs) has been part of clinical practice since the 1960s. These are usually reserved as end of line strategy. The inexorable rise in antimicrobial resistance (AMR) has demanded an urgent need for novel solutions for treatment of rUTIs [2-6]. Inappropriate use of broad-spectrum antibiotic treatments is considered to have largely contributed to this era of high resistance patterns [6]. Infections associated with such virulent pathogens have become increasingly difficult to manage and often require higher doses or alternative medications. A potential way forward has been the use of intravesical antibiotics (IVA), which have been shown to have greater effect on bacteria at a local level while reducing systemic absorption and its associated side effects [8-13].

In a study , a total of 63 patients with recuurent UTI’s were included.The mean number of UTIs reduced from 4.8 to 1.0 during intravesical treatment. The resistance rate of the uropathogens dropped from 78% to 23%. No systemic absorption or clinically relevant side-effects were observed[14].

In another study, a total of 22 patients with rUTI were taken. The proportion of multi-drug-resistant organisms in urine cultures decreased from 58.3% to 47.1% (p=0.04) and the rate of gentamicin resistance did not increase. Adverse events were mild and rare [13]

The aim of this study is to assess the effectiveness, feasibility and safety of intravesical gentamicin therapy in patients with recurrent urinary tract infections.

This Case series, Prospective study was conducted at Liaquat National Hospital and Medical College. The patients with recurrent urinary tract infections presenting into the urology OPD aged between 15 years and above with 3 or more positive urine cultures, Patients with neurogenic bladder, intermittent catheterization, symptomatic UTIS and multidrug resistance cultures were included in study. Data were compiled and analyzed using statistical package for social sciences (SPSS) version 26.

Total 69 patients were enrolled in current study. There was 44.9% of male and 55.1% female patients with mean age 41.69±15.89 years. Most common organisms were klebiella(52.2%), E Coli(27.5%) and gram negative bacilli(14.5%). In our study, multi drug resistance was found among 18(26.1%) patients while the effectiveness and safety was found among 89.9% and 94.2% respectively. We found significant association of multi drug resistance with hypertension (p=0.047) while significant mean difference was found for V.V with effectiveness.

A total of 69 patients were enrolled, including 31 (44.9%)
male and 38 (55.1%) females, with the mean age of
41.69±15.89 years. The most common past medical history
was C-section in 18 (26.1%) patients. It was observed that
14 (20.3%) patients had diabetes mellitus, 44 (63.8%) had
hypertension, and 24 (34.8%) had ischaemic heart disease
(IHD), while 11 (15.9%) had no known comorbidity (NKCM).
Most common organisms reported were Klebsiella in 36
(52.2%) patients, E. coli in 19 (27.5%) patients, and gramnegative bacilli in 10 (14.5%) patients. The median pre-void
residual was 280, median post-void residual (PVR) was 26,
median maximum flow (Q Max) was 20, median average
flow (Q Avg) was 11, and median voided volume (V.V) was
reported at 172. Detailed descriptive statistics are
presented in Table 1.
Inverted bladder wall thickness,seen in 11 (15.9%) patients,
was the most common ultrasonic kidney ureter bladder
(USG KUB) observation. Detailed frequency distribution of
USG KUB is presented in Table 2.
Multi drug resistance (MDR) was noted among 18 (26.1%)
patients. A borderline significant association of multi drug
resistance was reported with hypertension (p=0.047). No
significant association was noted between other patient
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Vol.74, No.1, January2024 Open Access
Table-1:Patients’characteristics (n = 69).
Characteristics n (%)
Gender
Male 31(44.9)
Female 38(55.1)
History
Angioplasty 10(14.5)
C-section 18(26.1)
Chest Infection 14(20.3)
ESWL(R) 12(17.4)
N/S 2(2.9)
TURP 13(18.8)
Comorbid
Diabetes 14(20.3)
Hypertension 44(63.8)
IHD 24(34.8)
NKCM 11(15.9)
Outcomes(↕Mean ± SD / Median (IQR))
Mean Age(years)↕ 41.69 ±15.89
Pre-void 280(120)
PVR 26(60)
Q Max 20(8)
Q Avg 11(3)
V.V 172(36)
Organism
E.coli 19(27.5)
Enterococcus 4(5.8)
Gramnegativebacilli 10(14.5)
Klebsiella 36(52.2)
Outcomes
Multidrugresistance 18(26.1)
Effectiveness 62(89.9)
Safety 65(94.2)
ESWL:extracorporeal shockwavelithotripsy; : Normal saline;TURP:Transurethral resection of
prostate; IHD: Ischemic heartdisease; NKCM: noknown co morbidity;PVR: post-voidresidual;
Q Max = maximum flow; Q Avg:average flow; V.V:voidedvolume.
Effectivenessandsafetyof intravesical Gentamicin therapyin patients with recurrent………
characteristics and MDR. The details are presented in
Table 3. The effectiveness was noted among 62 (89.9%)
patients. No significant association was reported between
patient characteristics and effectiveness

Conclusion
It can be concluded that treatment with IVA Gentamicin
may be helpful in reducing the frequency of episodes and
the need for oral antibiotics in patients with UTIs which
shows its effectiveness, and safety. However, more studies
are required to assess the long-term effectiveness of IVA
Gentamicin treatment in the said patient group

Malik RD, Wu YR, Christie AL, Alhalabi F, Zimmern PE. Impact of allergy and resistance on antibiotic selection for recurrent urinary tract infections in older women. Urol. 2018;113:26-33.
Linsenmeyer TA, Jain A, Thompson BW. Effectiveness of neomycin/polymyxin bladder irrigation to treat resistant urinary pathogens in those with spinal cord injury. J Spinal Cord Med. 1999;22(4):252-7.
Defoor W, Ferguson D, Mashni S, Creelman L, Reeves D, Minevich E, et al. Safety of gentamicin bladder irrigations in complex urological cases. J Urol. 2006;175(5):1861-4.