Abstract
Background/aim
Urinary tract infections remain one of the most common bacterial infections globally and are associated with a wide range of pathogens. This disease continues to be a significant public health concern, particularly in Pakistan and the district of Dera Ismail Khan (D.I.Khan). The current study was conducted to determine the frequency and antibiotic susceptibility profiles of bacterial isolates from patients with Urinary Tract Infections.
Materials and methods
This study was conducted from January 2022 to November 2024 in the district of D.I.Khan. A total of 610 individuals who were referred to or visited the Pathology Department of Gomal Medical College and Jamil Medical Lab for urine culture and sensitivity testing were included. All urine specimens were collected and processed under aseptic conditions.
Results
Of the 610 individuals, 260 (42.6%) had urine cultures positive for bacteria, while 350 (57.4%) showed no significant growth. Among the 260 positive cases, 105 (40.4%) were male and 155 (59.6%) were female. The highest frequency of infection was found in the older age group (> 60 years), accounting for 60 cases (23%). Among all isolates, E. coli (59.6%) was the most prevalent pathogen. Imipenem, nitrofurantoin, and fosfomycin were the most effective antimicrobial agents, while all pathogens exhibited 100% resistance to amoxicillin-clavulanic acid and ampicillin.
Conclusion
This study highlights the bacterial profile and increasing antimicrobial resistance in urinary tract infections, underscoring the need for regular surveillance and empirical treatment strategies.
Keywords: Urinary tract infections, Antimicrobial resistance, Antibiotic susceptibility, D.I.Khan, South Asia
Introduction
Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, occurring when pathogenic bacteria invade the normally sterile urinary system and proliferate, leading to inflammation and tissue damage [1]. These infections can affect any component of the urinary tract, including the urethra, bladder, and kidneys, with clinical manifestations ranging from mild dysuria to severe complications such as permanent kidney scarring [2].
UTIs represent a significant global health burden, with approximately 150 million cases occurring annually worldwide and associated healthcare costs exceeding $6 billion [3]. The condition disproportionately affects certain populations, including women of all ages, elderly men, and approximately 5% of girls and 2% of boys by age seven [2]. While over 95% of UTIs are caused by bacterial pathogens [4]the predominant causative organisms include Enterobacteriaceae species (Escherichia coli, Klebsiella, Proteus, Pseudomonas, and Enterobacter) and gram-positive cocci such as Staphylococcus saprophyticus and Enterococcus species [5].
Antibiotics have transformed modern medicine by saving millions of lives and making complex medical treatments possible. Before antibiotics were discovered, more than half of all deaths were caused by infectious diseases [6]. The implementation of antibiotics, combined with enhanced infection control measures, fundamentally transformed healthcare by enabling complex medical procedures and effectively treating previously fatal infections [7].
However, this therapeutic success has been increasingly threatened by the emergence of antimicrobial resistance (AMR). AMR occurs when bacteria evolve mechanisms that render antibiotics less effective or completely ineffective [8]leading to hundreds of thousands of deaths annually [9]. The rapid proliferation of multidrug-resistant bacterial strains has created a critical public health crisis, prompting the World Health Organization (WHO) to classify AMR among the top 10 global health threats facing humanity [10, 11]. This growing resistance undermines decades of medical progress and poses significant challenges for treating common infections that were once easily manageable.
The escalating incidence of UTIs worldwide necessitates comprehensive surveillance of causative bacterial pathogens and their antimicrobial resistance profiles. In resource-limited settings, empirical antibiotic therapy is frequently compromised by evolving resistance patterns among uropathogens, leading to treatment failures and increased healthcare burden. Pakistan, as a developing nation with limited antimicrobial stewardship programs, faces particular challenges in UTI management, with regional variations in resistance patterns requiring localized epidemiological data. District Dera Ismail Khan (D.I.Khan) represents an understudied population where current antimicrobial susceptibility data are insufficient to guide evidence-based therapeutic decisions.
This study was conducted to determine the bacterial etiology of UTIs and characterize the antimicrobial susceptibility patterns of isolated uropathogens in the D.I.Khan district. The objectives were to: (1) identify the frequency and distribution of bacterial species causing UTIs, and (2) evaluate the in vitro antimicrobial susceptibility profiles of these isolates against commonly prescribed antibiotics, thereby providing essential data to inform empirical treatment guidelines and antimicrobial stewardship initiatives in this region.
Materials and methods
Study area characteristics
This cross-sectional study was conducted in the Department of Pathology, Gomal Medical College, Dera Ismail Khan (D.I. Khan), Khyber Pakhtunkhwa (KPK), between January 2022 and November 2024. D.I. Khan, the 37th largest city in Pakistan, spans an area of 9,334 square kilometers with a population of approximately 1.69 million. Administratively, it is divided into six subdivisions: D.I. Khan, Daraban, Kulachi, Paharpur, Darazinda, and Paroa. Geographically, the district is bordered by Bhakkar and Dera Ghazi Khan (Punjab) to the east, South Waziristan to the southwest, Tank District to the northwest, and Lakki Marwat to the west, separated by the Sheikh Badin Hills. The district also lies close to the Koh-e-Sulaiman Mountain range near Balochistan.
Given its large population, diverse urban and rural settlements, and central healthcare facilities, D.I. Khan represents an important setting for detecting urinary tract infections. Patients from surrounding districts and remote areas often seek diagnostic services here, making it a representative site for studying the regional burden of UTIs and antimicrobial resistance patterns.
Sample collection and processing
A consecutive sampling method was employed to recruit 610 patients, whereby all eligible individuals presenting during the study period were enrolled without randomization. Participants comprised both male and female patients who presented to or were referred to the Pathology Department of Gomal Medical College and Jamil Medical Lab for routine urine culture and antimicrobial susceptibility testing. Fresh midstream urine specimens were collected using standard aseptic collection protocols.
Exclusion criteria included: (1) patients who had received antimicrobial therapy within the preceding seven days, and (2) individuals who declined to provide written informed consent. These exclusion parameters were implemented to ensure specimen validity and maintain ethical research standards.
Isolation and identification of bacterial culture
Urine specimens from all participants were processed using standard microbiological protocols. Each sample was aseptically inoculated onto three culture media: MacConkey agar, Cysteine Lactose Electrolyte Deficient (CLED) agar, and blood agar. The inoculated plates were incubated aerobically at 37 °C for 24 h under standard atmospheric conditions. Plates demonstrating no visible growth after the initial 24-hour incubation period were subjected to extended incubation for an additional 48 h before being reported as culture-negative.
All culture-positive specimens underwent comprehensive bacterial identification using a systematic approach that included: (1) evaluation of colony morphology and cultural characteristics, (2) Gram staining for bacterial classification, and (3) a standardized panel of biochemical tests. The biochemical identification panel comprised catalase test, oxidase test, Triple Sugar Iron (TSI) agar, Sulphur Indole Motility (SIM) medium, citrate utilization test, and urease test, supplemented with additional confirmatory tests as clinically indicated.
Testing for antimicrobial susceptibility pattern
Antimicrobial susceptibility of the isolates was determined on Mueller–Hinton agar using the Kirby–Bauer standard disc diffusion method, in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines, 2023 edition [12] The antimicrobial agents tested included Amoxicillin–Clavulanic acid, Trimethoprim/Sulfamethoxazole, Ceftriaxone, Cefixime, Ciprofloxacin, Amikacin, Nitrofurantoin, Fosfomycin, Imipenem, Cefoxitin, Doxycycline, Ampicillin, Vancomycin, Linezolid, Tigecycline, Cefoperazone–Sulbactam, and Piperacillin–Tazobactam.
For Gram-negative isolates, extended-spectrum β-lactamase (ESBL) production was confirmed using the phenotypic detection method as recommended by CLSI (2023), employing amoxicillin–clavulanic acid, ceftazidime, and cefotaxime discs [12].
Clinical trial number
Not applicable.
Data analyses
Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS). Chi-Square test was applied to determine significant associations between demographic categorical variables (e.g., gender, age group, diabetes status, and habitat). Antibiotic susceptibility data were analyzed descriptively and presented as frequencies and percentages.
Results
Six hundred ten urine samples received during the above periods of study, 260(42.6%) had urine culture positive for bacteria, while 350(57.4%) had showed no significant growth. Of the 260 positive patients, 105(40.4%) were male and 155(59.6%) were female. These patients were further divided in six age groups, the highest frequency was found in old age group > 60 years 60(23%), followed by 20–30 years of age 45(17%), while lowest positivity was observed in group < 10 years of age 20(8%). In our study, 68% of participants reported a history of diabetes, while 32% indicated no such history. Moreover, 159(61%) patients were from the rural areas, while 101(39%) from the Urban area (Table 1).
Table 1.
Demographic characteristics of urinary tract infections -positive culture patients, including distribution by sex, age groups, diabetic history, and habitat (n = 260)
| Factors | Details | N (%) | p-valve |
|---|---|---|---|
| Sex | Male | 105 (40.4%) | |
| Female | 155 (59.6%) | 0.04 | |
| Age (Years) | <10 | 20 (8%) | |
| 10-20 | 28 (11%) | ||
| 21-30 | 45 (17%) | ||
| 31-40 | 42 (16%) | ||
| 41-50 | 25 (10%) | ||
| 51-60 | 40 (15%) | ||
| >60 | 60 (23%) | 0.02 | |
| Diabetic history | Diabetic | 177(68%) | 0.01 |
| Non-diabetic | 83(32%) | ||
| Habitat | Urban | 31(12%) | |
| Rural | 229(88%) | 0.002 |
Among the 260 culture-positive cases, Escherichia coli was the most frequently isolated pathogen, 155 (59.6%), followed by Enterococcus spp., 30 (11.5%); Klebsiella pneumoniae, 27 (10.4%); Proteus mirabilis, 16 (6.2%); Pseudomonas aeruginosa, 15 (5.8%); Staphylococcus saprophyticus, 13 (5.0%); and Staphylococcus aureus, 4 (1.5%) (Table 2).
Table 2.
Frequency of bacterial isolates identified from urinary tract infections -positive patients, highlighting the predominance of Escherichia coli and distribution of other pathogens (n = 260)
| Isolates | N (%) |
|---|---|
| Escherichia coli | 155 (59.6) |
| Klebsiella pneumoniae | 27 (10.4) |
| Proteus mirabilis | 16 (6.2) |
| Pseudomonas aeruginosa | 15(5.8) |
| Enterococci spp. | 30 (11.5) |
| Staphylococcus saprophyticus | 13 (5) |
| Staphylococcus Aureus | 4 (1.5) |
| Total | 260 (100) |
From Tables 3, 4, 5, 6, 7, 8 and 9, antibiotic sensitivity and resistance patterns of gram-negative and gram-positive bacterial isolates obtained from urinary tract infection–positive patients are presented, highlighting multidrug resistance. Among gram-negative isolates, Proteus mirabilis showed 100% sensitivity to imipenem. E. coli showed 96% sensitivity to imipenem, 89% for Klebsiella pneumoniae, and 80% for Pseudomonas aeruginosa. A high level of susceptibility was also noted against fosfomycin: E. coli (87%), Klebsiella pneumoniae (81%), Pseudomonas aeruginosa (87%), and Proteus mirabilis (87%). Among gram-positive isolates, fosfomycin showed 100% sensitivity to Staphylococcus aureus, 87% to Enterococcus spp., and 85% to Staphylococcus saprophyticus. Nitrofurantoin also demonstrated good antimicrobial activity across both gram-negative and gram-positive isolates compared to other antibiotics such as ciprofloxacin, cephalosporins, amikacin, and macrolides.
Table 3.
Antimicrobial susceptibility pattern of Escherichia coli (n = 155)
| Antibiotic | Resistance n (%) | Sensitive n (%) |
|---|---|---|
| Amoxicillin-clavulanic acid | 155 (100%) | 0 (0%) |
| Cefoperazone-Sulbactam | 134 (86.5%) | 21 (13.5%) |
| Ciprofloxacin | 112 (72%) | 43 (28%) |
| Ceftriaxone | 124 (80%) | 31 (20%) |
| Amikacin | 44 (28%) | 111 (72%) |
| Imipenem | 6 (04%) | 149 (96%) |
| Tigecycline | 48 (31%) | 107 (69%) |
| Nitrofurantoin | 28 (18%) | 127 (82%) |
| Piperacillin-Tazobactam | 112 (72%) | 43 (28%) |
| Trimethoprim/sulfamethoxazole | 112 (72%) | 43 (28%) |
| Tetracycline | 52 (34%) | 103 (66%) |
| Fosfomycin | 20 (13%) | 135 (87%) |
| Ampicillin | 147 (95%) | 8 (5%) |
Table 4.
Antimicrobial susceptibility pattern of Klebsiella pneumonia (n = 27)
| Antibiotic | Resistance n (%) | Sensitive n (%) |
|---|---|---|
| Amoxicillin-clavulanic acid | 27 (100%) | 0 (0%) |
| Cefoperazone-Sulbactam | 19 (70%) | 8 (30%) |
| Ciprofloxacin | 24 (88%) | 3 (12%) |
| Ceftriaxone | 22 (81%) | 5 (19%) |
| Amikacin | 9 (33%) | 18 (67%) |
| Imipenem | 3 (11%) | 24 (89%) |
| Tigecycline | 24 (89%) | 3 (11%) |
| Nitrofurantoin | 7 (26%) | 20 (74%) |
| Piperacillin-Tazobactam | 18 (67%) | 9 (33%) |
| Trimethoprim/sulfamethoxazole | 19 (66%) | 8 (34%) |
| Tetracycline | 21 (82%) | 6 (18%) |
| Fosfomycin | 5 (19%) | 22 (81%) |
| Ampicillin | 27 (100%) | 0 (0%) |
Table 5.
Antimicrobial susceptibility pattern of Proteus mirabilis (n= 16)
| Antibiotic | Resistance n (%) | Sensitive n (%) |
|---|---|---|
| Amoxicillin-clavulanic acid | 16 (100%) | 0 (0%) |
| Cefoperazone-Sulbactam | 11 (68%) | 5 (32%) |
| Ciprofloxacin | 12 (75%) | 4 (25%) |
| Ceftriaxone | 9 (56%) | 7 (44%) |
| Amikacin | 4 (25%) | 12 (75%) |
| Imipenem | 0 (0%) | 16 (100%) |
| Piperacillin-Tazobactam | 12 (75%) | 4 (25%) |
| Trimethoprim/sulfamethoxazole | 11 (69%) | 5 (31%) |
| Tetracycline | 13 (81%) | 3 (19%) |
| Fosfomycin | 2 (13%) | 14 (87%) |
| Ampicillin | 16 (100%) | 0 (0%) |
Table 6.
Antimicrobial susceptibility pattern of Pseudomonas aeruginosa (n = 15)
| Antibiotic | Resistance n (%) | Sensitive n (%) |
|---|---|---|
| Amoxicillin-clavulanic acid | 15 (100%) | 0 (0%) |
| Cefoperazone-Sulbactam | 9 (60%) | 6 (40%) |
| Ciprofloxacin | 10 (67%) | 5 (33%) |
| Amikacin | 4 (27%) | 11 (73%) |
| Imipenem | 3 (20%) | 12 (80%) |
| Nitrofurantoin | 2 (13%) | 13 (87%) |
| Piperacillin-Tazobactam | 10 (67%) | 5 (33%) |
| Trimethoprim/sulfamethoxazole | 9 (60%) | 6 (40%) |
| Tetracycline | 11 (73%) | 4 (27%) |
| Fosfomycin | 2 (13%) | 13 (87%) |
| Ampicillin | 15 (100%) | 0 (0%) |
Table 7.
Antimicrobial susceptibility pattern of Enterococcus species (n = 30)
| Antibiotic | Resistance n (%) | Sensitive n (%) |
|---|---|---|
| Amoxicillin-clavulanic acid | 30(100%) | 0(0%) |
| Cefoperazone-Sulbactam | 20(67%) | 10(33%) |
| Ciprofloxacin | 24(80%) | 06(20%) |
| Ceftriaxone | 28(93%) | 02(07%) |
| Amikacin | 06(20%) | 24(80%) |
| Imipenem | 0(0%) | 30(100%) |
| Tigecycline | 07(23%) | 23(77%) |
| Nitrofurantoin | 06(20%) | 24(80%) |
| Piperacillin-Tazobactam | 29(97%) | 01(03%) |
| Trimethoprim/sulfamethoxazole | 04(13%) | 26(87%) |
| Linezolid | 16(53%) | 14(47%) |
| Fosfomycin | 04(13%) | 26(87%) |
| Ampicillin | 30(100%) | 0(0%) |
| Vancomycin | 20(67%) | 10(33%) |
| Cefoxitin | 21(70%) | 09(30%) |
Table 8.
Antimicrobial susceptibility pattern of Staphylococcus saprophyticus (n=13)
| Antibiotic | Resistance n (%) | Sensitive n (%) |
|---|---|---|
| Amoxicillin-clavulanic acid | 13(100%) | 0(0%) |
| Cefoperazone-Sulbactam | 8(62%) | 05(38%) |
| Ciprofloxacin | 02(15%) | 11(85%) |
| Ceftriaxone | 09(69%) | 04(31%) |
| Amikacin | 02(15%) | 11(85%) |
| Imipenem | 0(0%) | 13(100%) |
| Tigecycline | 03(23%) | 10(77%) |
| Nitrofurantoin | 0(0%) | 13(100%) |
| Piperacillin-Tazobactam | 10(77%) | 03(23%) |
| Trimethoprim/sulfamethoxazole | 04(31%) | 09(69%) |
| Linezolid | 02(15%) | 11(85%) |
| Fosfomycin | 02(15%) | 11(85%) |
| Ampicillin | 13(100%) | 0(0%) |
| Vancomycin | 8(62%) | 05(38%) |
| Cefoxitin | 10(77%) | 03(33%) |
Table 9.
Antimicrobial susceptibility pattern of Staphylococcus aureus (n=04)
| Antibiotic | Resistance n (%) | Sensitive n (%) |
|---|---|---|
| Amoxicillin-clavulanic acid | 4(100%) | 0(0%) |
| Cefoperazone-Sulbactam | 02(50%) | 02(50%) |
| Ciprofloxacin | 04(100%) | 0(0%) |
| Ceftriaxone | 03(75%) | 01(25%) |
| Amikacin | 0(0%) | 04(100%) |
| Imipenem | 0(0%) | 04(100%) |
| Nitrofurantoin | 0(0%) | 04(100%) |
| Piperacillin-Tazobactam | 04(100%) | 00(0%) |
| Trimethoprim/sulfamethoxazole | 01(25%) | 03(75%) |
| Linezolid | 04(100%) | 0(0%) |
| Ampicillin | 4(100%) | 0(0%%) |
| Vancomycin | 03(75%) | 01(25%) |
| Cefoxitin | 03(75%) | 01(25%) |
Discussion
Urinary tract infections (UTIs) continue to pose a major public health challenge in South Asia, where irrational prescribing practices and widespread self-medication with antibiotics have accelerated the emergence of resistant uropathogens. This rapid evolution of resistance patterns has created an urgent need for region-specific surveillance data to guide evidence-based therapy. The present study addresses this gap by providing the most up-to-date profiling of bacterial pathogens currently implicated in UTIs in our region, along with their resistance trends against commonly prescribed antibiotics. By presenting current demographic and antimicrobial susceptibility data, our findings offer valuable guidance for clinicians and policymakers in optimizing treatment strategies and curbing the rising threat of antimicrobial resistance.
UTIs remain one of the most common bacterial infections globally, particularly among women, and are associated with a wide range of pathogens, including both Gram-negative and Gram-positive bacteria. E. coli is the most frequently identified pathogen, but other organisms such as Klebsiella spp., Proteus spp., and Enterococcus spp. are also commonly implicated. The prevalence of multidrug-resistant (MDR) strains of uropathogens has been rising in recent years, posing significant challenges to effective treatment. In this study, we aimed to investigate the frequency and antimicrobial susceptibility patterns of bacterial isolates from patients with UTIs. The study showed 42.6% culture positivity for bacterial pathogens of UTIs in the human population of district D.I.Khan. This finding is supported by the opinions of some national and international researchers [13–16]. The demographic data reveal a higher prevalence of UTIs in females (59.6%) compared to males (40.4%), consistent with existing literature that attributes this to anatomical and physiological differences in the female urinary tract [4, 15, 17]. Age-wise, the highest infection rates were observed in individuals above 60 years (23%), followed by the 21–30 years age group (17%). These findings align with previous studies indicating increased susceptibility in postmenopausal women and sexually active younger women due to hormonal changes and behavioral factors [18]. Prostatic enlargement in men, accompanied by a decline in the bacteriostatic properties of prostatic secretions, may predispose to the development of urinary tract infections [2, 4, 18].
Additionally, the study revealed that 68% of UTI-positive patients had a history of diabetes, underscoring the well-established link between diabetes and an elevated risk of UTIs, likely due to impaired immune defenses and elevated glucose levels that favor bacterial proliferation [19, 20]. The present study found a higher frequency of UTIs in rural regions compared to urban areas. Possible contributing factors include limited access to healthcare services, low awareness, inadequate hygiene practices, socio-economic constraints such as poverty, and poor water quality or availability in rural settings. Similar trends have also been reported by other studies [21–23]. In our study, E. coli was the most frequently isolated microorganism, accounting for 59.6%, followed by Enterococcus spp. and Klebsiella pneumoniae. Additionally, organisms such as Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus saprophyticus, and Staphylococcus aureus were also detected. The predominance of E. coli in our study is consistent with earlier reports [24–27]. However, it has been noted that the range of bacterial uropathogens varies depending on the patient’s categorization and geographic region [28]. Notably, all isolates showed 100% resistance to ampicillin and amoxicillin–clavulanic acid, a finding consistent with previous reports [19, 29, 30]. The excessive and irrational use of antibiotics in the region may explain these alarming resistance rates. One important contributor is antibiotic self-medication, which is commonly practiced for a wide range of infections. The excessive and unreasonable use of antibiotics in this region is associated with the highest levels of resistance to ampicillin and amoxicillin-clavulanic acid.
One important process of bacterial resistance development is antibiotic self-medication, which is commonly used to treat a wide range of infections. Meropenem and nitrofurantoin demonstrated the highest activity against both Gram-positive and Gram-negative isolates; however, their accessibility remains limited. This correlates with several prior reports [18, 30]. In this study, fosfomycin (> 80%) was also recorded as the most active antibiotic against most of the uropathogens. This high rate of sensitivity is reported by various studies [31–33]. Among the Enterobacteriaceae Gram-negative bacterial isolates, 81.6% were ESBL producers. The highest proportion was observed in E. coli (73.5%), followed by Klebsiella pneumoniae (12.1%). This finding is consistent with a study conducted in Northern India [3]. Similarly, another study also reported comparable results [34].
Imipenem demonstrated very high susceptibility across all pathogens, with 96% susceptibility in E-Coli, 89% in Klebsiella pneumoniae, 100% in Proteus mirabilis, and 80% in Pseudomonas aeruginosa. It also showed 100% susceptibility in Gram-positive pathogens, including Enterococcus species, Staphylococcus saprophyticus, and Staphylococcus Aureus. Fosfomycin exhibited high susceptibility, particularly in E. coli and Proteus mirabilis (87% each), as well as in Klebsiella pneumoniae (81%), Enterococcus species (81%), and Staphylococcus saprophyticus (85%). Nitrofurantoin was highly effective against Gram-positive organisms, with 100% susceptibility in Staphylococcus saprophyticus and Staphylococcus Aureus, and 80% in Enterococcus species.
Although CLSI guidelines classify Proteus mirabilis as intrinsically resistant to tigecycline and nitrofurantoin, we nevertheless tested these agents to explore their potential activity profile in our region. Interestingly, while most isolates were resistant to tigecycline (81%), a small subset (19%) showed in-vitro susceptibility. Similarly, nitrofurantoin, generally considered inactive against Proteus, showed 87% apparent sensitivity in our isolates. These findings, though inconsistent with CLSI recommendations, highlight the complex behavior of local strains and suggest that further molecular and pharmacodynamic investigations may be warranted before completely excluding these drugs in certain clinical scenarios.
Amikacin demonstrated reasonably good activity against Gram-negative organisms, with 72% susceptibility in E-Coli, 67% in Klebsiella pneumoniae, and 75% in Proteus mirabilis, alongside excellent activity against Gram-positive pathogens, achieving 80% susceptibility in Enterococcus species and 85% in Staphylococcus saprophyticus. Fluoroquinolones, such as ciprofloxacin, showed moderate to low susceptibility overall, with only 28% susceptibility in E-Coli and 12% in Klebsiella pneumoniae. However, they were more effective in Gram-positive species like Staphylococcus saprophyticus (85%). Based on these findings, the most promising antibiotics for multidrug-resistant UTIs were imipenem, fosfomycin, and nitrofurantoin, owing to their high susceptibility rates against both Gram-positive and Gram-negative pathogens. Amikacin also demonstrated considerable effectiveness against Gram-negative infections.
The general principles for combination therapy involve starting with broad-spectrum combinations, such as imipenem and amikacin, for severe infections while awaiting culture and susceptibility results. Once the pathogen’s resistance profile is identified, therapy should be de-escalated to a more targeted approach to minimize the development of further resistance. Additionally, selecting combinations with synergistic mechanisms of action helps maximize bacterial killing while reducing the likelihood of resistance emergence, ensuring a more effective and sustainable treatment strategy. The choice of antibiotic combinations for treating MDR-UTIs is influenced by various factors, including the bacterial pathogen, its susceptibility profile, the severity of the infection, and patient-specific considerations. Based on the findings, several combinations could be considered as potentially effective against MDR pathogens.
For ESBL-producing Escherichia Coli, combinations such as imipenem with amikacin could provide broad-spectrum coverage and potent activity against Gram-negative bacteria. Fosfomycin combined with nitrofurantoin might be particularly suitable for uncomplicated UTIs in outpatient settings, while cefoperazone-sulbactam paired with amikacin could effectively address beta-lactamase-producing strains. These combinations may tackle ESBL resistance mechanisms, offering synergistic effects to enhance treatment outcomes.
Similarly, ESBL-producing Klebsiella pneumoniae might be managed effectively with combinations like imipenem and fosfomycin, which demonstrated strong efficacy. Piperacillin-tazobactam combined with amikacin could be a suitable choice for hospital-acquired infections, while tigecycline paired with fosfomycin might be recommended for severe or complicated cases. These combinations appear to integrate carbapenems or newer agents with adjunctive therapies, addressing the high resistance rates observed in Klebsiella pneumoniae infections.
For Proteus mirabilis, imipenem combined with amikacin could be highly effective against Gram-negative resistance. Fosfomycin and nitrofurantoin might offer a viable alternative for milder infections, especially when the use of carbapenems needs to be avoided. These combinations could ensure effective management of Proteus mirabilis infections while preserving potent agents for more severe cases.
MDR-Pseudomonas aeruginosa infections pose significant challenges, but combinations like imipenem with amikacin could remain a preferred choice for severe cases. Piperacillin-tazobactam combined with amikacin might also be effective for resistant Pseudomonas strains. In the case of Enterococcus spp., imipenem combined with linezolid could be particularly effective for severe infections, especially those caused by vancomycin-resistant Enterococcus (VRE). For uncomplicated or outpatient cases, nitrofurantoin paired with Fosfomycin might be a suitable option, while vancomycin combined with amikacin could be appropriate for infections susceptible to vancomycin. These combinations might provide comprehensive coverage for Gram-positive pathogens while addressing their specific resistance profiles. Infections caused by Staphylococcus saprophyticus and Staphylococcus Aureus might also benefit from tailored combination therapies. Imipenem with linezolid could be effective against methicillin-resistant Staphylococcus Aureus (MRSA) and MDR-Staphylococcus saprophyticus. For uncomplicated UTIs, fosfomycin combined with nitrofurantoin might be highly effective, whereas vancomycin paired with fosfomycin could be recommended for severe infections. These combinations might target Gram-positive MDR-pathogens, addressing specific resistance mechanisms to ensure optimal therapeutic outcomes. Overall, these tailored antibiotic combinations could provide a strategic approach to managing MDR-UTIs. The results of this study underline the critical role of antimicrobial stewardship in mitigating resistance. The high rates of ESBL production and multidrug resistance necessitate the judicious use of antibiotics, particularly beta-lactams and carbapenems. The observed effectiveness of fosfomycin and nitrofurantoin aligns with their continued recommendation for treating uncomplicated UTIs, emphasizing the need for their preservation through restricted use. The geographic and demographic disparities in UTI prevalence observed in this study underscore the influence of socio-economic and environmental determinants in disease prevention. The significantly higher burden in rural areas calls for targeted interventions, including improved sanitation, community education on personal hygiene, and enhanced access to healthcare facilities. Furthermore, the study highlights the role of rapid and accurate diagnostics, such as culture-based identification and susceptibility testing, in guiding rational therapy. Reliance on empirical treatment without laboratory confirmation risks worsening resistance trends, underlining the importance of diagnostic stewardship in clinical practice.
Conclusion
This study demonstrates the considerable burden of UTIs and the rising threat of antibiotic resistance in the D.I.Khan region. Our findings provide essential local data that can inform region-specific treatment guidelines and antimicrobial policies. Implementing robust antimicrobial stewardship programs, alongside sustained surveillance, is critical to ensuring better patient outcomes and curbing the spread of resistant pathogens.
Limitations
There are some limitations to this work. First, the design does not allow for tracking changes in resistance patterns across different time periods. Second, molecular analysis of resistance genes in ESBL-producing isolates was not performed, which could have helped explain the mechanisms behind resistance. Third, the findings are limited to a specific region and may not apply to other areas or populations. This study provides valuable regional data, and future research should focus on longitudinal tracking and molecular characterization to better understand resistance dynamics and the impact of interventions.
Acknowledgements
Along with all of the participants, we would like to thank Mr. Rehmat Ullah, Laboratory technician for all of his assistance.
Clinical trial
Not applicable.
Abbreviations
- AMR
Antimicrobial resistance
- AST
Antimicrobial Susceptibility Testing
- CLED
Cysteine Lactose Electrolyte Deficient
- CLSI
Clinical and Laboratory Standards Institute
- D.I. Khan
Dera Ismail Khan
- E-coli
Escherichia coli
- ESBL
Extended Spectrum Beta-Lactamase
- KPK
Khyber Pakhtunkhwa
- MDR
Multidrug-Resistant
- MRSA
Methicillin-Resistant Staphylococcus Aureus
- SPSS
Statistical Package for Social Sciences
- TSI
Triple Sugar Iron
- VRE
Vancomycin-Resistant Enterococcus
- WHO
World Health Organization
Authors’ contributions
ZU conceived and designed the study and drafted the initial manuscript. ZU and JA analyzed the data and carried out interpretations. ZU, NA, AQ, and AAA provided analytical support, while ZU, AU, MFF, AA, and SSS were involved in data collection and refinement. AAA, MFF, and AA secured funding. JA supervised, edited, and revised the manuscript. All authors read and approved the final version.
Funding
The authors extend their appreciation to Taif University, Saudi Arabia, for supporting this work through project number: TU-DSPP-2024-122.
Data availability
The datasets used in this study are available upon request. Please contact “Zahid Ullah” “ zahidwazir150@hotmail.com” for access to the data. All relevant materials and methods can be provided.
Declarations
Ethics approval and consent to participate
This study was approved by the Institutional Review Board (IRB) of Gomal Medical College (Approval No. 18/GJMS/JC). Written informed consent was obtained from all adult participants. For participants under the age of 16 years, informed consent was obtained from their parents or legal guardians. All methods were conducted in compliance with the relevant guidelines and regulations outlined in the Declaration of Helsinki.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
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References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used in this study are available upon request. Please contact “Zahid Ullah” “ zahidwazir150@hotmail.com” for access to the data. All relevant materials and methods can be provided.