Our study provides valuable insight on antimicrobial resistance among uropathogens in obstetrics and gynaecology patients from a northern Indian tertiary care hospital. Despite global concerns about antimicrobial resistance, research on resistance patterns in this specific patient group is limited. Most studies focus on general populations or specific healthcare settings, leaving gaps in understanding resistance trends in obstetrics and gynaecology domain. Our findings will be crucial for developing targeted antimicrobial stewardship strategy and microbiological report based treatment guidelines in our settings. Our susceptibility data for antibiotics like tetracyclines and fluoroquinolones are intended solely for surveillance and epidemiological interpretation and are not recommended for clinical use in pregnant patients.

Prevalence of uropathogens
The study identified 383 bacterial isolates from 5903 urine samples from both OPD and inpatients, 295 (77.02%) were isolated from OPD patients and 88 (22.97%) from IPD, with a predominance of Gram-negative bacteria, particularly E. coli. This aligns with previous study in India and Southeast Asia showing E. coli as the most common causative agent of UTI in both outpatient and inpatient settings.^9,10

Antimicrobial susceptibility patterns of Gram-negative bacteria
Nitrofurantoin, an oral chemotherapeutic agent, has been used in clinical practice since 1952. It is especially effective against uropathogens due to its broad-spectrum activity.¹¹ Susceptibility to E. coli showed (100% in OPD vs. 93.8% in IPD; p = 0.0289). A slight decline in nitrofurantoin susceptibility among IPD isolates raises concerns about its use in hospitalized settings. Overall, our data is in accordance to national AMR data which showed good susceptibility of 85.8% from urine samples in E. coli isolate.¹² Poor susceptibility in Klebsiella spp. was observed (0% in OPD vs. 25% in IPD). The lack of a comparable sample size between OPD and IPD has restricted us to assess the burden of resistance in IPD settings. A similar study based on 5 year retrospective data have demonstrated (6% in OPD vs 5% in IPD).¹³ Likewise, national AMR surveillance data for Klebsiella spp. in urine showed decreasing pattern susceptibility from 37.6% in 2017 to 36.7% in 2023.¹² Although, nitrofurantoin was recommended as a preferred drug in the 2010 international consensus guidelines for urinary tract infections.¹⁴ The study shows nitrofurantoin is largely ineffective against Klebsiella spp. and nitrofurantoin-resistant Klebsiella spp. should be suspected when patients fail empirical nitrofurantoin treatment. Our study data suggest avoiding nitrofurantoin as first-line empirical therapy for community-acquired UTIs in pregnant women until culture susceptibility results are available in these geographic settings.

Tetracycline was discovered in the late 1940s from Streptomyces aureofaciens and Streptomyces rimosus and function by blocking protein synthesis.¹⁵ In our study, doxycycline susceptibility of E. coli showed a significant decline in IPD isolates (60.2% in OPD vs. 38.9% in IPD; p = 0.0046). In contrast, doxycycline susceptibility in Klebsiella spp. showed no significant difference (73.9% in OPD vs. 66.7% in IPD). For Klebsiella spp. tetracycline susceptibility in IPD isolates was moderate at 66.7% with no available data for OPD isolates. A study has proposed doxycycline as an alternative treatment for UTI, especially for patients with limited oral options due to allergies or antibiotic-resistant organisms. However, the 2010 IDSA guidelines for uncomplicated cystitis and pyelonephritis do not recommend doxycycline as an oral treatment option for UTI.¹⁶

Cotrimoxazole, a combination of trimethoprim and sulfamethoxazole (160/800 mg) has been a first-line UTI therapy since the 1960s. It is effective against most Gram-negative and Gram-positive bacteria and taken orally twice daily for 3 days is the therapy of choice for UTIs in women.^14,17,18 Susceptibility in E. coli remained moderate and show no significant variation between OPD and IPD isolates (53.9% in OPD vs. 50% in IPD; p = 0.6712). A significant decline in susceptibility was observed in IPD isolates for Klebsiella spp. (84.8% in OPD vs. 66.7% in IPD). This study demonstrates that the susceptibility pattern of cotrimoxazole in the community was good (84.8%) indicating that cotrimoxazole can still be used for uncomplicated UTIs in outpatients in our geographic region.

Fosfomycin was discovered in Spain in 1969 and works by disrupting cell wall synthesis in both Gram-positive and Gram-negative bacteria.¹⁹ E. coli showed high susceptibility in both OPD and IPD isolates (100%; p = 1.0000). National survey has also documented high susceptibility in E. coli (93.7%) from urine isolates.¹²

Fluoroquinolones usage started in 1962 with the discovery of nalidixic acid, a by-product of chloroquine synthesis. Fluoroquinolones like ciprofloxacin and norfloxacin are widely used for treating UTIs because of their broad-spectrum activity and ability to penetrate tissues effectively.²⁰ However, resistance to these antibiotics are becoming a growing concern particularly among uropathogens. In E. coli isolates, ciprofloxacin and norfloxacin susceptibility decreased in IPD patients (35.5% in OPD vs 23.3% in IPD; p = 0.0860) and (50.3% in OPD vs 31.3% in IPD; p = 0.0093). National AMR surveillance for urine sample has also shown resistance to ciprofloxacin which ranged from 2.9%-33%.¹² This indicates widespread resistance among both community-acquired and hospital-acquired strains, with a more pronounced impact in hospital settings. For Klebsiella spp., ciprofloxacin susceptibility was notably higher in IPD isolates (72.7% in OPD vs. 100% in IPD), while norfloxacin susceptibility decreased in IPD isolates (91.2% in OPD vs. 75% in IPD).

Amoxicillin clavulanate was first introduced in 1981 to tackle the emerging β-lactamase-harbouring pathogens.²¹ The susceptibility to E. coli showed a significant decline in IPD (69.6% in OPD vs 42.9% in IPD; p = 0.0002). A notable reduction in susceptibility was also observed in Klebsiella isolates (65.2% in OPD vs 50% in IPD). These findings highlight that while beta-lactamase inhibitors remain effective for community-acquired infections, there is a significant rise in resistance within hospital settings particularly for E. coli and Klebsiella spp.

Aminoglycosides, introduced into clinical use in 1944 are potent, broad-spectrum antibiotics that act through inhibition of protein synthesis.²² Susceptibility to gentamicin were similar in E. coli isolates from both settings (75% in OPD vs. 78.1% in IPD; p = 0.7390), indicating no significant difference. High susceptibility to amikacin were observed in E. coli isolates (97% in OPD vs. 90.6% in IPD; p = 0.1338). Amikacin susceptibility in E. coli isolates from national AMR urine data has shown a decrease from 86.4% in 2017 to 71.1% in 2023.¹² Amikacin susceptibility and gentamicin susceptibility in Klebsiella spp. were slightly lower in OPD isolates (90.9% in OPD vs. 100% in IPD) and (93.8% in OPD vs. 100% in IPD). Geographic regional strains and antibiotic usage pressure dictates the variability in susceptibility. Judicious use of aminoglycosides and stringent antimicrobial stewardship has to be incorporated to prevent resistance, since national data on amikacin susceptibility has shown a decrease from 56.9% to 44.4% over a period of 7 years in Klebsiella spp.¹²

Third-generation cephalosporins, such as cefotaxime and ceftazidime are particularly effective against Gram-negative bacteria. They are often prescribed for infections resistant to earlier-generation cephalosporins or other β-lactam antibiotics.²³ Susceptibility of cefotaxime and ceftazidime for E. coli decreased in IPD isolates (47.3% in OPD vs. 19.4% in IPD; p = 0.0001) and (61.5% in OPD vs. 25% in IPD; p = 0.0001). This low susceptibility in 3^rd generation cephalosporin has also been observed in a nationwide surveillance among E. coli from urine isolates.¹² In Klebsiella spp., cefotaxime susceptibility was lower in IPD isolates (75.8% in OPD vs. 50% in IPD) and ceftazidime showed 100% susceptibility in IPD isolates (73.7% in OPD vs. 100% in IPD). Although, decreasing susceptibility to Klebsiella spp. for cefotaxime and ceftazidime over 7 years period has been documented from national surveillance (27.3%-21.9% and 23.4%-17.9%).¹² Decades of overuse and misuse have led to widespread resistance in third-generation cephalosporins which make these antibiotics less effective and nearly unusable as empiric therapy in seriously ill patients in tertiary care practices.

Carbapenems are highly potent, broad-spectrum antibiotics and their unique structure makes them resistant to most β-lactamase enzymes, including metallo-β-lactamases (MBL) and extended-spectrum β-lactamases (ESBL).^24,25 Imipenem became the first carbapenem introduced in 1985 for treating complex infections.²⁶ In our study, imipenem susceptibility to E. coli showed 100% in OPD and IPD isolates. Meropenem also performed well with a slight non-significant difference in susceptibility (100% in OPD vs. 95% in IPD; p = 0.0594) (Table 2). For Klebsiella spp., there was a stark contrast in susceptibility to carbapenems. Imipenem showed 85.7% effectiveness in OPD isolates but was completely ineffective in IPD (0%). This highlights the emergence of carbapenem-resistant Klebsiella strains in hospitals, likely due to the selective pressure of higher antibiotic use. The rising worldwide trend in CRE infections has been attributed to high mortality and morbidity among vulnerable populations in a hospital setting.^27,28

Table 2:
Comparison of antimicrobial susceptibility pattern of Gram-negative bacteria in urine samples between obstetrics and gynaecology OPD and IPD

NR-Not recommended according to CLSI; ND-not done; p < 0.05 was considered significant.

FDA approved the use of piperacillin tazobactam combination (β-lactam/β-lactamase inhibitor) in 1993 to treat patients with moderate to severe infections caused by piperacillin resistant, piperacillin tazobactam susceptible β-lactamase producing strains of bacteria.²⁹ Susceptibility to E. coli showed a significant decline in IPD isolates compared to OPD isolates (96.3% in OPD vs 44.8% in IPD; p = 0.0001). The declining trend in E. coli susceptibility to piperacillin-tazobactam has been observed from national surveillance studies which showed 73.7% in 2017 to 56.1% in 2023.¹² A notable reduction in susceptibility was also observed in Klebsiella spp. isolates dropping significantly in IPD isolates (90.9% in OPD vs 33.3% in IPD). Klebsiella spp. decreasing susceptibility to piperacillin-tazobactam from 52.5% in 2017 to 46.7% in 2023 has been observed in national surveillance survey from urine sample.¹² These findings highlight that while beta-lactamase inhibitors remain effective for community-acquired infections, there is a significant rise in resistance within hospital settings particularly for E. coli and Klebsiella spp.

Gram-positive bacteria
Enterococcus species exhibited universal susceptibility to vancomycin, linezolid, and teicoplanin (100%) in both OPD and IPD isolates. However, penicillin G showed no effectiveness in IPD isolates (100% vs 0%). Similarly, ampicillin was 100% susceptible compared to IPD isolates (33.3%). Nitrofurantoin displayed high and stable susceptibility in both OPD and IPD isolates (75%). Doxycycline susceptibility was moderate in OPD isolates (50%) but significantly reduced in IPD isolates (16.7%). High-level gentamicin (HLG) susceptibility decreased in IPD isolates (50% in OPD vs. 25% in IPD) (Table 3).

Staphylococcus aureus shows excellent susceptibility (100%) to key agents like nitrofurantoin, gentamicin, linezolid, teicoplanin, vancomycin in OPD and IPD settings
(Table 3). However, resistance to Penicillin G and cefoxitin indicates methicillin-resistant strains, necessitating caution in empirical therapy. Staphylococcus saprophyticus showed universal susceptibility of 100% in both OPD and IPD isolates for nitrofurantoin, gentamicin, teicoplanin, linezolid and vancomycin (Table 3).

Table (3):
Comparison of antimicrobial susceptibility pattern of Gram-positive bacteria in urine samples between obstetrics and gynaecology OPD and IPD

NR-Not recommended according to CLSI; ND-Not done; p < 0.05 was considered significant.

The marked differences in susceptibility patterns between OPD and IPD isolates have important implications for empiric management of UTIs in obstetrics and gynaecology. In OPD settings, nitrofurantoin and fosfomycin remain reliable empiric options for E. coli; however, the complete resistance of Klebsiella spp. to nitrofurantoin underscores the need for culture-based confirmation when this pathogen is suspected. In IPD settings, broader resistance across multiple antibiotic classes, including significant reductions in susceptibility to β-lactam/β-lactamase inhibitors, fluoroquinolones, and third-generation cephalosporins, limits the utility of conventional oral agents. The absence of carbapenem susceptibility in IPD Klebsiella spp. isolates further highlights emerging hospital-acquired multidrug-resistance. These findings emphasize the need for setting-specific empiric guidelines with routine culture and susceptibility testing particularly critical in hospitalized patients.