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Article

Antibiotic Outcomes of Enterococcal Urinary Tract Infections: A Retrospective Analysis from Saudi Arabia and Oman

by
Abrar K. Thabit
1,*,
Juhaina S. Al-Maqbali
2,3,
Khaled F. Alharthi
4,
Salem M. Baotab
4,
Abdullah M. Bankhar
4,
Rayyan M. Wali
4,
Mohammed O. Alzahrani
4,
Asiya K. Alharthi
5,
Taqwa M. Alhamsaidi
5,
Ibrahim Al Busaidi
6,
Ahmad J. Mahrous
7 and
Jimmy Jose
5
1
Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah 22254, Saudi Arabia
2
Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Science, Sultan Qaboos University, Muscat 123, Oman
3
Department of Pharmacy, Sultan Qaboos University Hospital, University Medical City, Muscat 123, Oman
4
Faculty of Pharmacy, King Abdulaziz University, Jeddah 22254, Saudi Arabia
5
School of Pharmacy, University of Nizwa, Nizwa 616, Oman
6
Department of Medicine, Sultan Qaboos University Hospital, University Medical City, Muscat 123, Oman
7
Department of Pharmaceutical Practice, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia
*
Author to whom correspondence should be addressed.
Pathogens 2026, 15(3), 250; https://doi.org/10.3390/pathogens15030250
Submission received: 4 February 2026 / Revised: 24 February 2026 / Accepted: 24 February 2026 / Published: 26 February 2026
(This article belongs to the Special Issue Challenges of Multidrug-Resistant Bacteria and Drug Development of Antibacterials)
Versions Notes

Abstract

Background: Enterococcus species are involved in urinary tract infections (UTIs), and they are known to be intrinsically resistant to certain antibiotics. We aimed to investigate the clinical characteristics and treatment outcomes of enterococcal UTIs in three hospitals in Saudi Arabia and Oman. Methods: A retrospective cohort study was conducted on adults with clinically and microbiologically confirmed enterococcal UTI based on urinary symptoms and a urine culture of ≥100,000 CFU/mL, who received an antibiotic active against the pathogen. The primary endpoint was clinical cure. Secondary endpoints included microbiological cure, length of stay (LOS), in-hospital mortality, and recurrence. Results: E. faecalis and E. faecium were isolated from 188 (67.1%) and 92 (32.9%), respectively, of 280 included patients. Ampicillin/amoxicillin (25%) and vancomycin (22.1%) were the most-used antibiotics. Compared with E. faecium, E. faecalis was associated with higher clinical cure rates (75% vs. 57.6%; p = 0.003), lower in-hospital mortality (15.7% vs. 38.5%; p < 0.0001), and shorter LOS (12.5 vs. 25 days; p < 0.0001). No difference in recurrence was observed. Ciprofloxacin was associated with high odds of clinical cure (OR, 4.28; 95% CI, 1.18–15.56). Conversely, the recent cancer chemotherapy and growth of Enterococcus at another site were associated with lower odds of clinical cure. Urinary catheter removal was associated with lower recurrence odds (OR, 0.48; 95% CI, 0.24–0.98). Conclusions: This study highlights the clinical challenges posed by enterococcal UTIs, particularly by E. faecium. Ciprofloxacin remains an effective option, particularly against E. faecalis. Patients with advanced age, critical illness, complicated infections, and liver disease, as well as patients on hemodialysis, require close monitoring to improve outcomes.

1. Introduction

Enterococci are Gram-positive chain-like cocciform bacteria that are normally present in the gastrointestinal tract and function commensally with humans [1,2]. However, they are associated with a wide variety of infections, such as urinary tract infections (UTIs), bacteremia, and endocarditis, which often require hospitalization [1,2]. Two species cause the majority of enterococcal infections: Enterococcus faecalis and E. faecium [3].
Enterococci have developed several mechanisms to evade the effects of commonly used antibiotics. As the resistance of Enterococci to commonly used antibiotics (such as vancomycin) is on the rise, alternative antibiotics are being considered. Treatment options for UTIs caused by Enterococci include oral agents, such as amoxicillin and nitrofurantoin, as well as parenteral agents, such as ampicillin, vancomycin, teicoplanin, quinupristin/dalfopristin, gentamicin, linezolid, and daptomycin [4]. However, these options are not always feasible due to patient factors (e.g., potential adverse effects that may aggravate a patient’s condition, such as nephrotoxicity with vancomycin and thrombocytopenia with linezolid), cost, and local unavailability. Enterococci are known to be intrinsically resistant to some antimicrobials, such as cephalosporins, clindamycin, and trimethoprim/sulfamethoxazole [4]. A plastic genome allows these two significant species of Enterococci to readily acquire resistance to more antibiotics, such as high-level aminoglycoside resistance, high-level ampicillin resistance, and vancomycin resistance, either through mutation or by horizontal transfer of genetic elements conferring resistance determinants [3]. Furthermore, Enterococci can acquire resistance to other antimicrobials after exposure or through the transfer of resistance genes from the same or other bacterial species. Such acquired resistance can be developed against vancomycin, β-lactams, aminoglycosides, erythromycin, fluoroquinolones, tetracycline, rifampin, nitrofurantoin, and chloramphenicol [5,6]. Enterococcal infections may be difficult to treat and present ongoing therapeutic challenges to clinicians worldwide because of their broad spectrum of intrinsic resistance and tolerance to the bactericidal activity of many agents, combined with their prodigious ability to acquire resistance to available antibiotics [3].
A previous study from Saudi Arabia evaluated the clinical characteristics of patients with enterococcal UTIs, finding that a non-intensive care unit (ICU) admission, recent exposure to antibiotics within the last three months, and the presence of a urinary catheter were prevalent among the patients [7]. Furthermore, despite a lower prevalence of E. faecium infections compared with E. faecalis infections, a comparison between the two species in terms of clinical outcomes revealed that infections with E. faecium were associated with higher levels of inflammatory markers (namely C-reactive protein), higher mortality, and longer hospital stays, due to variations in virulence factors or increased rates of antibiotic resistance in E. faecium as opposed to E. faecalis [7]. In terms of comparing antibiotic therapy outcomes, very few studies compared treatment options for enterococcal UTIs. Nonetheless, one retrospective cohort study compared the effectiveness of linezolid and non-linezolid antibiotics (including nitrofurantoin) in the treatment of UTIs caused by vancomycin-resistant Enterococci (VRE) and found no significant difference in clinical cure rates between the two groups [8]. An in vitro study found that the susceptibility rates of Enterococcus spp. isolates from clinical urine samples to nitrofurantoin and linezolid were 65% and 100%, respectively [9].
Due to the limited number of studies comparing different treatment options for UTIs caused by Enterococcus spp., this study aimed to evaluate the outcomes of the two major Enterococcus species, assess the outcomes of different antibiotics, and identify predictors associated with clinical cure and other clinical outcomes.

2. Materials and Methods

2.1. Study Design

This retrospective multicenter cohort study included adult patients who were admitted to or visited an outpatient clinic at King Abdulaziz University Hospital in Jeddah, Saudi Arabia, King Abdullah Medical City in Makkah, Saudi Arabia, and Sultan Qaboos University Hospital in Muscat, Oman, between June 2012 and December 2022, had clinically and microbiologically confirmed enterococcal UTI, and received antibiotic therapy. All patients who were available during the study period were pre-screened for eligibility using the electronic medical record system.

2.2. Study Population

The inclusion criteria for the study were patients aged 18 years or older who had a urine culture positive for E. faecalis or E. faecium with a colony count of ≥105 CFU/mL, with symptoms of upper or lower urinary tract infection (fever, flank or back pain, nausea and/or frequency, dysuria, urgency, nocturia, and/or suprapubic pain), and received definitive antibiotic therapy targeting Enterococci as outpatients, during hospitalization, or upon discharge from the hospital. The cutoff value of bacterial load of 105 CFU/mL was selected based on an established microbial threshold for bacteriuria [10]. Patients with incomplete data and those who received meropenem for therapy were excluded as meropenem has weak in vitro activity against Enterococci [11]. Only the first infection was considered in patients with recurrent enterococcal UTI.
All microbiological methods for bacterial culturing followed the guidelines of Clinical Laboratory Standards Institute (CLSI) [12]. Bacterial identification was carried out using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (by bioMérieux, Marcy-l’Étoile, France, in King Abdulaziz University Hospital and by Bruker Corp., Billerica, MA, USA, in King Abdullah Medical City and Sultan Qaboos University Hospital). This was followed by antibiotic susceptibility testing that was conducted using automated methods, including VITEK2 (bioMérieux, Marcy-l’Étoile, France) in King Abdulaziz University Hospital and King Abdullah Medical City and BD Phoenix™ (Franklin Lakes, NJ, USA) in Sultan Qaboos University Hospital. Minimum inhibitory concentration (MIC) interpretation in all participating hospitals followed CLSI guidelines (document M-100-S32), where Enterococcus spp. were considered resistant at or above the following MIC values: 16 µg/mL for ampicillin, 32 µg/mL for vancomycin, 8 µg/mL for levofloxacin, and 128 µg/mL for nitrofurantoin [12]. These MIC breakpoints did not change over the study period (2012–2022).

2.3. Clinical Outcomes and Definitions

The primary outcomes included clinical cure (defined as the resolution of signs and symptoms of UTI at the end of therapy). As such, treatment failure involved persistence of symptoms requiring a change in antibiotic therapy or death. For outpatients, this was assumed if patients did not return complaining of a lack of improvement or a recurrence. Microbiological cure was defined as the eradication of initial bacteriuria in the follow-up urine culture if available. The secondary outcomes included in-hospital mortality, defined as death during hospitalization for inpatients (as such, death was not recorded for outpatients). The length of hospital stay (LOS) was defined as the number of days from admission to discharge for surviving hospitalized patients. Recurrence was categorized as either relapse or reinfection. Relapse was defined as infection with the same organism isolated in the index culture within two weeks after therapy completion, whereas reinfection was defined as infection with an organism different from that of the index culture within or after two weeks of therapy completion, infection with the same organism as in the index culture more than two weeks after therapy completion, or a sterile intervening culture (defined as lack of bacterial growth between two UTI episodes while the patient is off antibiotics and is asymptomatic [i.e., after achieving microbiological cure]) [13,14]. Complicated UTI factors were defined by the presence of certain factors, such as structural or functional abnormality of the urinary tract, pregnancy, or prolonged symptoms, as described previously [15]. Polymicrobial cultures were defined as the presence of one or more organisms along with the Enterococcus strain that is considered pathogenic (i.e., not a contaminant, such as yeast and Streptococcus agalactiae) [16]. Examples of organisms that were considered potentially pathogenic include members of the Enterobacterales family (such as Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, etc.) and Pseudomonas aeruginosa.
Antibiotic therapy targeting Enterococci was administered intravenously or orally using one of the following agents: ampicillin (or amoxicillin), vancomycin, daptomycin, ciprofloxacin, piperacillin/tazobactam, linezolid, or nitrofurantoin.

2.4. Statistical Analysis

Patients were divided into two groups depending on the species (E. faecalis and E. faecium groups). Categorical variables were presented as frequencies and percentages and were compared using the Chi-square test or Fisher’s exact test (when the frequency was less than five times), while continuous variables were expressed using the median and interquartile range (IQR), as they were determined to be not normally distributed with the Shapiro–Wilk test of normality. The Mann–Whitney test was used to compare the continuous variables between the two groups. However, in the subgroup analyses, the Kruskal–Wallis test was used to compare the outcomes of each antibiotic against each species. The two-tailed significance threshold was set at p < 0.05.
To assess the impact of different factors on clinical outcomes, multivariable regression was performed on factors with p < 0.05 in the univariate analysis. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were reported. Significance was assessed using the omnibus test of model coefficients, and the goodness-of-fit of the model was assessed using the Hosmer–Lemeshow test. All statistical analyses were performed using SPSS version 24.0 (IBM Corp., Armonk, NY, USA).
A total sample size of 263 patients was needed to achieve a power of 90% considering an effect size of 20% in the difference of clinical cure between the two Enterococcal species and an α-error probability of 5%. The effect size was determined based on a low probability estimate due to the lack of such studies in the literature. Sample size calculation was done using G*Power version 3.1.9.7 (University of Dusseldorf, Dusseldorf, Germany).

2.5. Ethical Declarations

This study was approved by the Institutional Review Board of King Abdullah Medical City (approval number: 23-1031; date 15 January 2023) and the Medical and Research Ethics Committee of the College of Medicine and Health Sciences, SQU, Muscat, Oman (approval number: MREC #3198; SQU-EC/321/2023; dated 9 January 2024). Informed consent was waived given the retrospective nature of the study.

3. Results

3.1. Baseline Characteristics

A total of 280 patients were included, with a median age of 62.5 years [IQR, 41.2–74.9], and more than half (57.1%) were female. E. faecalis and E. faecium were isolated from 188 (67.1%) and 92 (32.9%) patients, respectively. As listed in Table 1, most baseline characteristics were balanced between the two groups based on the species, except for patients’ location as outpatients or inpatients, distribution of the sites where Enterococcus spp. was isolated, and the antibiotic therapy used. Approximately one-third of the total cohort (n = 57; 32.2%) had secondary bacteremia. Among the 15 ICU patients, six (40%) had bacteremia, and two of them died. Additionally, more E. faecium isolates compared to E. faecalis isolates were resistant to ampicillin (82.6% vs. 8.5%), vancomycin (32.6% vs. 1.1%), and nitrofurantoin (52.2% vs. 1.6%%) with a p < 0.0001 for all comparisons. However, no difference was observed in rates of resistance to levofloxacin. The growth of organisms other than Enterococci was more prevalent with E. faecium than with E. faecalis (42.4% vs. 28.2%; p = 0.017).

3.2. Outcomes of Patients

Table 2 shows the clinical outcomes of enterococcal UTIs stratified by species. More than two-thirds of the patients in the overall cohort achieved clinical (69.3%) and microbiological cure (67.5%). For the latter, 169 of 280 patients had follow-up urine cultures (i.e., 111 patients did not have follow-up cultures). Both clinical cure and bacterial eradication rates were significantly higher with E. faecalis than with E. faecium (75% vs. 57.6% and 74.1% vs. 54.4%; p = 0.003 and 0.010, respectively). Moreover, patients infected with E. faecalis compared with E. faecium patients had lower in-hospital mortality rates (15.7% vs. 38.5%; p < 0.0001) and shorter median LOS (12.5 vs. 25 days; p < 0.0001). However, no difference was observed in recurrence or recurrence types (relapse or reinfection).

3.3. Subgroup Analysis Based on Enterococcal Species

In the subgroup analysis of patients with E. faecalis (Table 3), clinical cure rates were only numerically the highest with ciprofloxacin (n = 29/33; 87.9%), nitrofurantoin (n = 14/16; 87.5%), piperacillin/tazobactam (n = 16/21; 76.2%), and ampicillin or amoxicillin (n = 51/67; 76.1%), with a p value of 0.064. The median duration of therapy ranged from 6 to 8 days (p = 0.017). Statistically significant variations were observed between the antibiotics and in-hospital mortality and recurrence rates. In terms of E. faecium infections, all patients treated with ampicillin or amoxicillin (n = 3), piperacillin/tazobactam (n = 5), and ciprofloxacin (n = 4) achieved clinical cure, which was statistically significant with a p value of 0.012 (Table 4). While no difference was observed in microbiological cure, duration of therapy, and recurrence rates, a significant difference (p < 0.0001) was observed in the median LOS (the shortest duration was 0.5 days with ampicillin or amoxicillin and 6 days with ciprofloxacin) and in-hospital mortality (p = 0.019).

3.4. Factors Associated with Different Outcomes

The p values of the univariate analysis of the association of factors with each clinical outcome are provided in Table S1. Bacteremia was one of the evaluated factors that was not associated with any outcome; thus, it was not included in the multivariable analysis of all outcomes. Results of the multivariable logistic regression for clinical cure, microbiological cure, in-hospital mortality, and recurrence are presented in Table 5. The analysis revealed that the use of ciprofloxacin and having a risk factor for complicated UTI were associated with odds of clinical cure of 4.28 and 3.78 (95% CI, 1.18–15.56 and 1.33–10.77; p = 0.028 and 0.013, respectively). In contrast, recent exposure to cancer chemotherapy, the growth of Enterococci in cultures other than the urine culture (mostly bacteremia), and use of vancomycin for therapy were associated with lower odds of clinical cure (OR, 0.18, 0.41, and 0.46; 95% CI, 0.07–0.52, 0.17–0.97, and 0.22–0.98; p = 0.001, 0.042, and 0.044, respectively). While admission to the inpatient medical floor was associated with higher odds of bacterial eradication (OR, 3.27; 95% CI 1.18–9.08; p = 0.023), female sex, resistance to ampicillin, and polymicrobial culture were associated with lower odds of bacterial eradication (OR, 0.34, 0.31, and 0.43; 95% CI, 0.16–0.76, 0.10–0.97, and 0.20–0.93; p = 0.008, 0.044, and 0.032, respectively). Furthermore, the odds of in-hospital mortality increased with advancing age (OR, 1.03; 95% CI 1.01–1.04; p = 0.007) and admission to the ICU (OR, 5.55; 95% CI, 1.45–21.34; p = 0.013). Lastly, only removal of the urinary catheter was associated with lower odds of recurrence (OR, 0.48; 95% CI, 0.24–0.98; p = 0.044), whereas treatment with ampicillin was associated with higher odds of recurrence (OR, 2.94; 95% CI, 1.40–6.17; p = 0.005).

4. Discussion

This study offers critical insights into the clinical characteristics, resistance patterns, and treatment outcomes of enterococcal UTIs, with a particular focus on comparing the outcomes of infections with E. faecalis and E. faecium. The higher prevalence of E. faecalis in our study compared with E. faecium corroborates previous reports of enterococcal UTIs [17,18,19]. Our findings emphasized poorer clinical outcomes of UTI caused by E. faecium, which was previously reported in terms of lower clinical and microbiological cure rates, higher in-hospital mortality rates, and longer hospital stays [7]. However, the results of the multivariable regression analysis showed no difference in outcomes between the two species.
Our study revealed that the median age of patients with enterococcal UTIs was 63 years, a finding consistent with other studies, such as that by Kajihara et al., where the average patient age was 64.6 years [20]. However, a significant variability in age demographics was observed across studies. For example, Barros et al. reported a younger average age of 48.9 years in their cohort [21], while a multinational study by Turjeman et al. found that over 60% of patients were between 55 and 75 years old [18]. This suggests that the age distribution of enterococcal infections may vary significantly depending on population characteristics, healthcare settings, and geographical factors.
The gender distribution in our study also differed from some prior research. While several studies, including those by Barros et al. and Turjeman et al. reported a male predominance in enterococcal infections [18,21], our study found that 57.9% of the patients were female. This discrepancy can be explained by the higher susceptibility of females to UTIs due to anatomical factors, such as a shorter urethra and proximity of the urethral opening to the vaginal and rectal areas, facilitating bacterial translocation to the urinary tract. This is consistent with the general understanding that women are more prone to UTIs overall, although male predominance has been noted in specific populations with hospital-acquired infections or in patients with complex comorbidities.
A key finding of our study is the difference in clinical outcomes and resistance patterns between E. faecalis and E. faecium infections. The clinical cure rate was significantly higher with E. faecalis compared with E. faecium. On the contrary, the mortality rate was significantly lower with E. faecalis than with E. faecium. This is consistent with findings from a study by Álvarez-Artero et al., who found that the OR of mortality in the case of UTIs due to E. faecalis was 0.1 (95% CI, 0.1–0.3; p = 0.0001) [17]. The poorer outcomes associated with E. faecium observed in the current and previous studies may be attributed to the higher rates of resistance to commonly used antibiotics. For example, in our study, E. faecium exhibited a strikingly high resistance rate to ampicillin, moderate resistance to vancomycin, and moderate resistance to nitrofurantoin compared with E. faecalis, which exhibited very low resistance rates to these antibiotics. Such a resistance pattern by E. faecium makes the treatment of UTIs caused by this organism more challenging. This finding mirrors global trends, since E. faecium is known for its multidrug resistance, particularly in hospital settings, where vancomycin-resistant E. faecium poses a significant clinical challenge [22]. This underscores the importance of early identification and aggressive treatment of E. faecium infections, particularly in vulnerable populations. The findings related to antibiotic resistance, particularly the high resistance of E. faecium to ampicillin and vancomycin, reflect global concerns about the rising prevalence of VRE. Previous reports have highlighted the clinical and economic burdens posed by VRE, resulting in prolonged hospital stays, increased healthcare costs, and higher mortality rates [6]. The results of our study reinforce the urgent need for improved antimicrobial stewardship and infection control measures, particularly in healthcare settings where VRE is more prevalent. The rising resistance of E. faecium to key antibiotics, such as vancomycin, underscores the necessity for species-specific treatment strategies, as E. faecalis and E. faecium exhibit distinctly different resistance patterns and clinical outcomes. Another potential explanation for the high mortality rate in the E. faecium group is the numerically high rate of cardiovascular and kidney diseases among the patients.
In our study, in-hospital mortality was reported in 23.2% of hospitalized patients. Although the cause of mortality was not captured from the patients’ medical records in our study, we evaluated several factors for their potential association with this outcome. While 32.2% of the total cohort in our study had bacteremia, this factor was not significantly associated with mortality. Conversely, increasing age and ICU admission illustrated a significant association in the multivariable analysis. Our study also revealed that 40% of the ICU patients had secondary bacteremia, where two incidents were fatal. In a study by Suppli et al., hospitalization in the ICU was associated with 4.2 odds of 30-day all-cause mortality of patients with enterococcal bacteremia (95% CI, 1.7–10; p = 0.002) [23]. This could be attributed to the fact that many patients in the ICU tend to have multiple comorbidities and varying hemodynamics [24]. In addition, older age was found to be an independent predictor of mortality in patients with enterococcal bacteremia (hazards ratio, 1.02; p = 0.005) [25]. Notably, numerous previous studies have demonstrated that enterococcal bacteremia is associated with mortality rates exceeding 20% [23,25,26,27].
In terms of recurrence, a study by Salm et al. evaluated outpatient males and reported a recurrence rate of enterococcal UTI reaching 25.9% compared to 22.2% with Escherichia coli, a common cause of UTIs (p < 0.001) [28]. The reason behind the relatively high recurrence rate reported by Salm et al. and in our study could be explained from a microbiological perspective, where Enterococci have been shown to have the capacity to live within urothelial cells of the ascending urinary tract. Horsley et al. confirmed the shedding of the E. faecalis within the urothelial cells of patients with chronic UTIs [29]. Moreover, a study on a mouse model using E. faecium demonstrated the capacity of the organism to form biofilms on the urothelial surface of the urinary tract, which could also form on indwelling catheters [30]. This virulence factor may explain why urinary catheter removal was significantly associated with lower odds of recurrence in our study.
Our study also highlights important differences in the effectiveness of various antibiotics in treating E. faecalis and E. faecium infections. For E. faecalis, ciprofloxacin and nitrofurantoin (for cystitis only) were most associated with higher clinical cure rates. Previous studies, including those by Swaminathan and Alangaden, have also reported that E. faecalis is generally more susceptible to first-line antibiotics like nitrofurantoin and amoxicillin [4]. Conversely, among patients with E. faecium infections, treatment with ciprofloxacin and piperacillin/tazobactam was associated with favorable outcomes, with both achieving 100% clinical cure rates, whereas vancomycin treatment was associated with a high mortality rate. However, such results should be carefully interpreted given the small sample number of patients who received these three antibiotics (4, 5, and 29, respectively). Moreover, the effectiveness of newer agents, such as linezolid and daptomycin, especially for E. faecium, which had notable success in previous studies, should be considered as part of the therapeutic arsenal against this multidrug-resistant organism. Linezolid, in particular, has shown promise in treating VRE infections (clinical cure rate reaching 71.4% in our study); however, its use should be judicious to prevent the emergence of resistance. The variability in treatment outcomes between the two species, particularly the poor response to vancomycin by E. faecium, highlights the need for ongoing research into alternative therapeutic options and tailored antibiotic protocols based on local resistance patterns.
Several factors were evaluated for their potential association with major clinical outcomes, including clinical cure, microbiological cure, and in-hospital mortality. Two factors were positively associated with clinical cure, including ciprofloxacin use and the presence of a risk factor for a complicated UTI, which had approximately four times the odds of achieving clinical cure. Ciprofloxacin has long been known to be well excreted in the urine and was associated with good clinical outcomes in treating both upper and lower UTIs due to Gram-positive and Gram-negative organisms [31,32]. Moreover, in the subgroup analysis, patients who received ciprofloxacin also experienced shorter LOS than those who received its antibiotic counterparts. Nevertheless, only a few patients in the E. faecium group received ciprofloxacin compared with the number of patients in the E. faecalis group. This may explain the inflated OR that favors this agent for enterococcal UTI treatment. Notably, a review article spanning 10 years that evaluated antimicrobial resistance found that the average overall susceptibility rate of E. faecalis to ciprofloxacin was 67% [33].
Patients with a risk factor for a complicated UTI tended to receive antibiotics with high rates of clinical cure (>70%), such as piperacillin/tazobactam, ampicillin, and ciprofloxacin, which explains their positive association with clinical cure. The high odds of clinical cure associated with complicated UTI could be possibly explained by more extensive management, which may have included catheter removal (i.e., source control), since 59.3% of the total cohort had a urinary catheter at the time of UTI diagnosis, and about two-thirds (64.5%) had their catheter removed. Cancer chemotherapy within three months and growth of Enterococcus spp. in another non-urine sample were associated with negative odds of clinical cure. This can be explained by the immunosuppression state and a high rate of antimicrobial resistance in cancer patients as well as the isolation of Enterococcus from other sites, including the blood [34,35,36].
Liver disease and polymicrobial culture were negatively associated with bacterial eradication. This can be attributed to the use of broad-spectrum antibiotic therapy in polymicrobial infections, which are potentially less potent against Enterococcus spp. than other organisms, such as meropenem or cefepime. A previous study found that a high proportion of patients with liver disease had indwelling catheters inserted, which increased the risk of bacteriuria by 5–10% each day [37]. Interestingly, among the 25 patients with liver disease in our study, 15 (60%) had catheters inserted. In our study, a urine culture was considered polymicrobial only if the coexisting organism (or organisms) is (or are) potentially pathogenic and not commonly known as a urine contaminant, such as yeast or Streptococcus agalactiae, based on a consensus developed by Moreland et al. [16]. Furthermore, a comprehensive review by Gaston et al. concluded that the presence of multiple microbes in the urinary tract can facilitate dynamic intermicrobial interactions, such as enhanced mutagenesis and production of toxins or adhesins [38]. These microbial consortia can augment the virulence of the pathogens, resulting in increased disease severity.
Five factors were associated with more than one odds of in-hospital mortality: advanced age, ICU admission, liver disease, hemodialysis, and receiving vancomycin for treatment. Overall, patients with chronic liver disease and those on hemodialysis are known to have an increased risk of mortality due to their vulnerability to severe infections and the development of antibiotic resistance following frequent exposures to antibiotics [37,39,40]. The potential emergence of vancomycin resistance during therapy may have contributed to the high mortality observed in patients who received vancomycin. While this was not specifically evaluated in our study, it was assumed based on findings from previous clinical reports [41,42,43]. In our study, the overall mortality rate in patients who received vancomycin was 40.32% (25 of 62 patients).
Although our study provided important insights into the clinical characteristics and treatment outcomes of enterococcal UTIs considering the differences between the two major species, a few limitations should be considered when interpreting the results. The retrospective nature of the study resulted in the lack of some clinical data, such as follow-up microbiological culture results. Moreover, the heterogeneity of the patients being included from outpatients and inpatients, as well as including both upper and lower UTIs, should also warrant careful interpretation of the results. The reasons behind in-hospital mortality were not evaluated; thus, we could not count the number of patients who died of UTI, as some patients may have died due to other underlying comorbidities, especially considering the high rate of cardiovascular and kidney diseases in our patient cohort, where we found numerically high rates of mortality in patients with these conditions, as well as in patients with liver disease and cancer. Additionally, the previous history of recent antibiotic exposure was only documented based on data available in the medical records of patients. Hence, receiving antibiotics from other sources (such as primary healthcare clinics) could not be captured. Moreover, antibiotic susceptibility testing methods and antibiotic panels varied among the participating hospitals; thus, only the susceptibility patterns to the antibiotics commonly used in clinical practice by all three hospitals were reported in this study without reporting the exact MIC values, since two of the participating hospitals only include MIC interpretation in their culture and susceptibility reports. Furthermore, although the study included three hospitals from three large cities in Saudi Arabia and Oman, the results may not be generalizable to other hospitals in the Gulf region or to hospitals located in small cities or rural areas. Lastly, some patients had polymicrobial urinary cultures, where the coexisting pathogens may have had a potential influence on outcomes, though such patients were included in the study cohort to align with the patient population encountered in standard clinical practice.

5. Conclusions

This study underscores the clinical burden of enterococcal UTIs, particularly those caused by E. faecium. Although the findings revealed that patients infected with E. faecium had poorer clinical outcomes than those infected with E. faecalis, possibly due to higher rates of antibiotic resistance, the multivariable analysis demonstrated no difference in outcomes. Ciprofloxacin remains an effective option against E. faecalis in particular. It was also effective in the four patients who were infected with E. faecium. However, nitrofurantoin (for cystitis only), ampicillin or amoxicillin, and piperacillin/tazobactam were effective against E. faecalis only. On the other hand, ampicillin or amoxicillin, piperacillin/tazobactam, and linezolid were effective against E. faecium despite the small number of patients who received them. Of note, close monitoring should be considered for elderly patients, patients receiving chemotherapy, patients with complicated infections (i.e., those with a second culture from a different site growing Enterococcus spp.), critically ill patients in the ICU, patients with underlying liver disease, and patients on hemodialysis to improve their outcomes. Our findings suggest that vancomycin should be used cautiously in enterococcal UTIs, with repeat susceptibility testing in case of inadequate clinical response to assess the possible development of resistance during therapy. Similar attention should be given to ampicillin or amoxicillin in patients prone to recurrent infections. Finally, urinary catheter removal should be prioritized in patients with indwelling catheters to reduce the risk of recurrence. Future research is warranted to assess the incidence of antimicrobial resistance development by Enterococci during therapy and to elucidate the potential underlying mechanisms.

Supplementary Materials

The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/pathogens15030250/s1. Table S1 (p values of univariate analysis of the association of different factors with clinical outcomes) on the results of the univariate analysis is included in the Supplementary Materials.

Author Contributions

Conceptualization, Methodology, Formal Analysis, Supervision, Writing—Review and Editing: A.K.T. Supervision, Writing—Review and Editing: J.S.A.-M. and J.J. Data Curation, Investigation, Writing—Original Draft: K.F.A., S.M.B., A.M.B., R.M.W., M.O.A., A.K.A. and T.M.A. Supervision, Writing—Review and Editing: A.J.M. Writing—Review and Editing: I.A.B. and A.J.M. All authors have read and agreed to the published version of the manuscript.

Funding

The project was funded by KAU Endowment (WAQF) at King Abdulaziz University, Jeddah, Saudi Arabia. The authors, therefore, acknowledge with thanks WAQF and the Deanship of Scientific Research (DSR) for technical and financial support.

Institutional Review Board Statement

This study was approved by the Institutional Review Board of King Abdullah Medical City (approval number: 23-1031; date 15 January 2023) and the Medical and Research Ethics Committee of the College of Medicine and Health Sciences, SQU, Muscat, Oman (approval number: MREC #3198; SQU-EC/321/2023; dated 9 January 2024).

Informed Consent Statement

Informed consent was waived given the retrospective nature of the study.

Data Availability Statement

Data associated with this study are available from the corresponding author upon request.

Acknowledgments

We would like to thank Atheer Alsehli, Israa Idris, Manar Badwood, Waad Alharbi, and Malak Almatrafi for their help with the data collection. This study was presented at the International Congress on Infectious Diseases (ICID) in December 2024, Cape Town, South Africa (abstract no. 103).

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
CFIColony-forming unit
CIConfidence interval
ICUIntensive care unit
IQRInterquartile range
LOSLength of stay
OROdds ratio
UTIUrinary tract infection
VREVancomycin-resistant Enterococci

References

  1. Levitus, M.; Rewane, A.; Perera, T.B. Vancomycin-Resistant Enterococci. In StatPearls; StatPearls: Treasure Island, FL, USA, 2022. [Google Scholar]
  2. Raza, T.; Ullah, S.R.; Mehmood, K.; Andleeb, S. Vancomycin resistant Enterococci: A brief review. J. Pak. Med. Assoc. 2018, 68, 768–772. [Google Scholar]
  3. Garcia-Solache, M.; Rice, L.B. The Enterococcus: A Model of Adaptability to Its Environment. Clin. Microbiol. Rev. 2019, 32, e00058-18. [Google Scholar] [CrossRef] [PubMed]
  4. Swaminathan, S.; Alangaden, G.J. Treatment of resistant enterococcal urinary tract infections. Curr. Infect. Dis. Rep. 2010, 12, 455–464. [Google Scholar] [CrossRef] [PubMed]
  5. Butt, T.; Leghari, M.J.; Mahmood, A. In-vitro activity of nitrofurantoin in enterococcus urinary tract infection. J. Pak. Med. Assoc. 2004, 54, 466–469. [Google Scholar]
  6. Thabit, A.K.; Crandon, J.L.; Nicolau, D.P. Antimicrobial resistance: Impact on clinical and economic outcomes and the need for new antimicrobials. Expert Opin. Pharmacother. 2015, 16, 159–177. [Google Scholar] [CrossRef] [PubMed]
  7. Alharthi, K.F.; Baotob, S.M.; Bankhar, A.M.; Alsehli, A.A.; Idris, I.A.; Badawood, M.S.; Alharbi, W.K.; Almatrafi, M.M.; Mahrous, A.J.; Thabit, A.K. Characteristics and outcomes of urinary tract infections caused by Enterococci: A multicenter retrospective study from two tertiary hospitals in Saudi Arabia. J. Infect. Chemother. 2024, 30, 1190–1193. [Google Scholar] [CrossRef]
  8. Wingler, M.J.; Patel, N.R.; King, S.T.; Wagner, J.L.; Barber, K.E.; Stover, K.R. Linezolid for the Treatment of Urinary Tract Infections Caused by Vancomycin-Resistant Enterococci. Pharmacy 2021, 9, 175. [Google Scholar] [CrossRef]
  9. Jain, S.; Gupta, J. A Study on Susceptibility Pattern of Nitrofurantoin in Clinical Isolates of Enterococcus: A Study on Susceptibility Pattern of Nitrofurantoin in Clinical Isolates of Enterococcus. Natl. J. Integr. Res. Med. 2018, 8, 53–56. [Google Scholar]
  10. Nicolle, L.E. Urinary tract infections in the elderly. Clin. Geriatr. Med. 2009, 25, 423–436. [Google Scholar] [CrossRef]
  11. Edwards, J.R. Meropenem: A microbiological overview. J. Antimicrob. Chemother. 1995, 36, 1–17. [Google Scholar] [CrossRef]
  12. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: Thertieth Informational Supplement [Document M100-S32]; National Committee for Clinical Laboratory Standards: Wayne, PA, USA, 2022. [Google Scholar]
  13. Dason, S.; Dason, J.T.; Kapoor, A. Guidelines for the diagnosis and management of recurrent urinary tract infection in women. Can. Urol. Assoc. J. 2011, 5, 316–322. [Google Scholar] [CrossRef]
  14. Hooton, T.M. Recurrent urinary tract infection in women. Int. J. Antimicrob. Agents 2001, 17, 259–268. [Google Scholar] [CrossRef]
  15. Wagenlehner, F.M.E.; Bjerklund Johansen, T.E.; Cai, T.; Koves, B.; Kranz, J.; Pilatz, A.; Tandogdu, Z. Epidemiology, definition and treatment of complicated urinary tract infections. Nat. Rev. Urol. 2020, 17, 586–600. [Google Scholar] [CrossRef] [PubMed]
  16. Moreland, R.B.; Brubaker, L.; Wolfe, A.J. Polymicrobial urine cultures: Reconciling contamination with the urobiome while recognizing the pathogens. Front. Cell. Infect. Microbiol. 2025, 15, 1562687. [Google Scholar] [CrossRef]
  17. Alvarez-Artero, E.; Campo-Nunez, A.; Garcia-Garcia, I.; Garcia-Bravo, M.; Cores-Calvo, O.; Galindo-Perez, I.; Pendones-Ulerio, J.; Lopez-Bernus, A.; Belhassen-Garcia, M.; Pardo-Lledias, J. Urinary tract infection caused by Enterococcus spp.: Risk factors and mortality. An observational study. Rev. Clin. Esp. 2021, 221, 375–383. [Google Scholar] [CrossRef]
  18. Turjeman, A.; Babich, T.; Pujol, M.; Carratala, J.; Shaw, E.; Gomila-Grange, A.; Vuong, C.; Addy, I.; Wiegand, I.; Grier, S.; et al. Risk factors for enterococcal urinary tract infections: A multinational, retrospective cohort study. Eur. J. Clin. Microbiol. Infect. Dis. 2021, 40, 2005–2010. [Google Scholar] [CrossRef]
  19. Goel, V.; Kumar, D.; Kumar, R.; Mathur, P.; Singh, S. Community Acquired Enterococcal Urinary Tract Infections and Antibiotic Resistance Profile in North India. J. Lab. Physicians 2016, 8, 50–54. [Google Scholar] [CrossRef] [PubMed]
  20. Kajihara, T.; Nakamura, S.; Iwanaga, N.; Oshima, K.; Takazono, T.; Miyazaki, T.; Izumikawa, K.; Yanagihara, K.; Kohno, N.; Kohno, S. Clinical characteristics and risk factors of enterococcal infections in Nagasaki, Japan: A retrospective study. BMC Infect. Dis. 2015, 15, 426. [Google Scholar] [CrossRef] [PubMed]
  21. Barros, M.; Martinelli, R.; Rocha, H. Enterococcal urinary tract infections in a university hospital: Clinical studies. Braz. J. Infect. Dis. 2009, 13, 294–296. [Google Scholar] [CrossRef][Green Version]
  22. Zhou, X.; Willems, R.J.L.; Friedrich, A.W.; Rossen, J.W.A.; Bathoorn, E. Enterococcus faecium: From microbiological insights to practical recommendations for infection control and diagnostics. Antimicrob. Resist. Infect. Control 2020, 9, 130. [Google Scholar] [CrossRef]
  23. Suppli, M.; Aabenhus, R.; Harboe, Z.B.; Andersen, L.P.; Tvede, M.; Jensen, J.U. Mortality in enterococcal bloodstream infections increases with inappropriate antimicrobial therapy. Clin. Microbiol. Infect. 2011, 17, 1078–1083. [Google Scholar] [CrossRef] [PubMed]
  24. Thomas-Ruddel, D.O.; Frohlich, H.; Schwarzkopf, D.; Bloos, F.; Riessen, R. Sepsis and underlying comorbidities in intensive care unit patients: Analysis of the cause of death by different clinicians-a pilot study. Med. Klin. Intensivmed. Notfmed. 2024, 119, 123–128. [Google Scholar] [CrossRef] [PubMed]
  25. Zerbato, V.; Pol, R.; Sanson, G.; Suru, D.A.; Pin, E.; Tabolli, V.; Monticelli, J.; Busetti, M.; Toc, D.A.; Croce, L.S.; et al. Risk Factors for 30-Day Mortality in Nosocomial Enterococcal Bloodstream Infections. Antibiotics 2024, 13, 601. [Google Scholar] [CrossRef] [PubMed]
  26. McBride, S.J.; Upton, A.; Roberts, S.A. Clinical characteristics and outcomes of patients with vancomycin-susceptible Enterococcus faecalis and Enterococcus faecium bacteraemia—A five-year retrospective review. Eur. J. Clin. Microbiol. Infect. Dis. 2010, 29, 107–114. [Google Scholar] [CrossRef]
  27. Pinholt, M.; Ostergaard, C.; Arpi, M.; Bruun, N.E.; Schonheyder, H.C.; Gradel, K.O.; Sogaard, M.; Knudsen, J.D.; Danish Collaborative Bacteraemia, N. Incidence, clinical characteristics and 30-day mortality of enterococcal bacteraemia in Denmark 2006–2009: A population-based cohort study. Clin. Microbiol. Infect. 2014, 20, 145–151. [Google Scholar] [CrossRef]
  28. Salm, J.; Salm, F.; Arendarski, P.; Kramer, T.S. High frequency of Enterococcus faecalis detected in urinary tract infections in male outpatients—A retrospective, multicenter analysis, Germany 2015 to 2020. BMC Infect. Dis. 2023, 23, 812. [Google Scholar] [CrossRef]
  29. Horsley, H.; Malone-Lee, J.; Holland, D.; Tuz, M.; Hibbert, A.; Kelsey, M.; Kupelian, A.; Rohn, J.L. Enterococcus faecalis subverts and invades the host urothelium in patients with chronic urinary tract infection. PLoS ONE 2013, 8, e83637. [Google Scholar] [CrossRef]
  30. Sillanpaa, J.; Nallapareddy, S.R.; Singh, K.V.; Prakash, V.P.; Fothergill, T.; Ton-That, H.; Murray, B.E. Characterization of the ebp(fm) pilus-encoding operon of Enterococcus faecium and its role in biofilm formation and virulence in a murine model of urinary tract infection. Virulence 2010, 1, 236–246. [Google Scholar] [CrossRef]
  31. Wagenlehner, F.M.; Kinzig-Schippers, M.; Sorgel, F.; Weidner, W.; Naber, K.G. Concentrations in plasma, urinary excretion and bactericidal activity of levofloxacin (500 mg) versus ciprofloxacin (500 mg) in healthy volunteers receiving a single oral dose. Int. J. Antimicrob. Agents 2006, 28, 551–559. [Google Scholar] [CrossRef]
  32. Xue, Z.; Xiang, Y.; Li, Y.; Yang, Q. A systematic review and meta-analysis of levofloxacin and ciprofloxacin in the treatment of urinary tract infection. Ann. Palliat. Med. 2021, 10, 9765–9771. [Google Scholar] [CrossRef]
  33. Thabit, A.K.; Alabbasi, A.Y.; Alnezary, F.S.; Almasoudi, I.A. An Overview of Antimicrobial Resistance in Saudi Arabia (2013–2023) and the Need for National Surveillance. Microorganisms 2023, 11, 2086. [Google Scholar] [CrossRef] [PubMed]
  34. Nanayakkara, A.K.; Boucher, H.W.; Fowler, V.G., Jr.; Jezek, A.; Outterson, K.; Greenberg, D.E. Antibiotic resistance in the patient with cancer: Escalating challenges and paths forward. CA Cancer J. Clin. 2021, 71, 488–504. [Google Scholar] [CrossRef]
  35. Delgado, A.; Guddati, A.K. Infections in Hospitalized Cancer Patients. World J. Oncol. 2021, 12, 195–205. [Google Scholar] [CrossRef]
  36. Scharloo, F.; Cogliati Dezza, F.; Lopez-Hernandez, I.; Martinez Perez-Crespo, P.M.; Goikoetxea Aguirre, A.J.; Perez-Rodriguez, M.T.; Fernandez-Suarez, J.; Leon Jimenez, E.; Moran Rodriguez, M.A.; Fernandez-Natal, I.; et al. Clinical characteristics, predisposing factors and outcomes for Enterococcus faecalis versus Enterococcus faecium bloodstream infections: A prospective multicentre cohort study. Eur. J. Clin. Microbiol. Infect. Dis. 2024, 43, 2011–2022. [Google Scholar] [CrossRef]
  37. Bajaj, J.S.; O’Leary, J.G.; Wong, F.; Reddy, K.R.; Kamath, P.S. Bacterial infections in end-stage liver disease: Current challenges and future directions. Gut 2012, 61, 1219–1225. [Google Scholar] [CrossRef] [PubMed]
  38. Gaston, J.R.; Johnson, A.O.; Bair, K.L.; White, A.N.; Armbruster, C.E. Polymicrobial interactions in the urinary tract: Is the enemy of my enemy my friend? Infect. Immun. 2021, 89, e00652-20. [Google Scholar] [CrossRef]
  39. Chandrashekar, A.; Ramakrishnan, S.; Rangarajan, D. Survival analysis of patients on maintenance hemodialysis. Indian. J. Nephrol. 2014, 24, 206–213. [Google Scholar] [CrossRef]
  40. de Arriba, G.; Avila, G.G.; Guinea, M.T.; Alia, I.M.; Herruzo, J.A.; Ruiz, B.R.; Tejeiro, R.D.; Rubio, M.E.L.; Poyatos, C.V.; Roldan, C.G. Mortality of hemodialysis patients is associated with their clinical situation at the start of treatment. Nefrologia 2021, 41, 461–466. [Google Scholar] [CrossRef]
  41. O’Toole, R.F.; Leong, K.W.C.; Cumming, V.; Van Hal, S.J. Vancomycin-resistant Enterococcus faecium and the emergence of new sequence types associated with hospital infection. Res. Microbiol. 2023, 174, 104046. [Google Scholar] [CrossRef]
  42. Li, G.; Walker, M.J.; De Oliveira, D.M.P. Vancomycin Resistance in Enterococcus and Staphylococcus aureus. Microorganisms 2022, 11, 24. [Google Scholar] [CrossRef] [PubMed]
  43. Al-Maqbali, J.S.; Shukri, Z.A.; Sabahi, N.A.; Al-Riyami, I.; Al Alawi, A.M. Vancomycin Therapeutic Drug Monitoring (TDM) and Its Association with Clinical Outcomes: A Retrospective Cohort. J. Infect. Public Health 2022, 15, 589–593. [Google Scholar] [CrossRef] [PubMed]
Table 1. Baseline characteristics of patients with enterococcal urinary tract infections.
Table 1. Baseline characteristics of patients with enterococcal urinary tract infections.
Characteristic
n (%) Unless Specified Otherwise		All Patients
(n = 280)		Enterococcus faecalis
(n = 188)		Enterococcus faecium
(n = 92)		p Value
Age (years); median [IQR]62.5 [41.2–74.9]61.9 [41.8–73.4]65.3 [39.9–79.7]0.212
Gender (female)160 (57.1)106 (56.4)54 (58.7)0.713
Location
Outpatient54 (19.3)45 (23.9)9 (9.8)0.005
Non-ICU inpatient211 (75.4)133 (70.7)78 (84.8)0.010
ICU15 (5.4)10 (5.3)5 (5.4)0.968
UTI site 0.165
Upper/pyelonephritis 123 (43.9)88 (46.8)35 (38)
Lower/cystitis157 (56.1)100 (53.2)57 (62)
Comorbidities
Diabetes 144 (51.4)100 (53.2)44 (47.8)0.399
Dyslipidemia 43 (15.4)28 (14.9)15 (16.3)0.758
Thyroid disease 30 (10.7)22 (11.7)8 (8.7)0.445
Kidney disease 133 (47.5)87 (46.3)46 (50)0.558
Liver disease 22 (7.9)15 (8)7 (7.6)0.914
Cardiovascular disease 188 (67.1)123 (65.4)65 (70.7)0.382
Cancer 42 (15)29 (15.4)13 (14.1)0.776
Solid organ transplant 9 (3.2)4 (2.1)5 (5.4)0.141
Bone marrow transplant 1 (0.4)01 (1.1)0.152
Hemodialysis 24 (8.6) 12 (6.4)12 (13)0.086
Recent hospitalization * 129 (46.1)85 (45.2)44 (47.8)0.680
Recent antibiotic use *113 (40.4)73 (38.8)40 (43.5)0.456
Recent chemotherapy * 25 (8.9)17 (9)8 (8.7)0.924
Recent immunosuppressant use * 32 (11.4) 24 (12.8)8 (8.7)0.315
Having a risk factor for complicated UTI 256 (91.4)174 (92.6)82 (89.1)0.337
Other risk factors for complicated UTI 0.488 **
Structural or functional abnormality of urinary tract59 (21.1)45 (23.9)14 (15.2)
Genitourinary obstruction19 (6.8)15 (8)4 (4.3)
Prolonged symptoms (>7 days) 19 (6.8)12 (6.4)7 (7.6)
Pregnancy7 (2.5)6 (3.2)1 (1.1)
Nosocomial or nursing home-acquired infection8 (2.3)5 (2.7)3 (3.3)
Urinary catheter at baseline166 (59.3)104 (55.3)62 (67.4)0.053
Antibiotic resistance
Ampicillin92 (32.9)16 (8.5) 76 (82.6)<0.0001
Vancomycin32 (11.5)2 (1.1)30 (32.6)<0.0001
Nitrofurantoin51 (18.2)3 (1.6)48 (52.2)<0.0001
Levofloxacin87 (31.1)53 (28.2)34 (37)0.137
Polymicrobial culture92 (32.9)53 (28.2)39 (42.4)0.017
Other enterococcal culture47 (16.9)33 (17.7)14 (15.2)0.597
Other enterococcal culture site 0.044 **
Blood57 (32.2)44 (39.3)13 (20)
Respiratory9 (5.1)4 (3.6)5 (7.7)
Skin or soft tissue2 (1.1)02 (3.1)
Body fluid4 (2.3)2 (1.8)2 (3.1)
Cerebrospinal fluid1 (0.5)1 (0.9)0
Urinary catheter removed (n = 166)107 (64.5)70 (67.3)37 (59.7)0.320
Antibiotic therapy <0.0001 **
Ampicillin or amoxicillin70 (25)67 (35.6)3 (3.3)
Vancomycin62 (22.1)33 (17.6)29 (31.5)
Daptomycin46 (16.4)17 (9)29 (31.5)
Ciprofloxacin37 (13.2)33 (17.6)4 (4.3)
Piperacillin/tazobactam26 (9.3)21 (11.2)5 (5.4)
Linezolid22 (7.9)1 (0.5)21 (22.8)
Nitrofurantoin17 (6.1)16 (8.5)1 (1.1)
Duration of antibiotic therapy (days); median [IQR]7 [5–9]7 [5–8]7 [5–10]0.363
ICU, intensive care unit; IQR, interquartile range; UTI, urinary tract infection. * Within 3 months of presentation. ** The p value is for the collective comparison of all the items included in this subheading.
Table 2. Outcomes of patients with enterococcal urinary tract infections.
Table 2. Outcomes of patients with enterococcal urinary tract infections.
Outcome
n (%) Unless Specified Otherwise		All Patients
(n = 280)		Enterococcus faecalis
(n = 188)		Enterococcus faecium
(n = 92)		p Value
Clinical cure194 (69.3)141 (75)53 (57.6)0.003
Microbiological cure (n = 169) *114 (67.5)83 (74.1)31 (54.4)0.010
In-hospital mortality (n = 257) **61 (23.7)26 (15.7)35 (38.5)<0.0001
Length of stay (days); median [IQR] (n = 240)15.5 [7–32]12.5 [6–22]25 [10–54]<0.0001
Recurrence (n = 276)88 (31.9)62 (33.5)26 (28.6)0.408
Recurrence type 0.670
Relapse30 (34.1)22 (35.5)8 (30.8)
Reinfection58 (65.9)40 (64.5)18 (69.2)
IQR, interquartile range. * For patients with available follow-up urine cultures. ** Outpatients were excluded.
Table 3. Treatment outcomes of patients infected with Enterococcus faecalis (n = 188) *.
Table 3. Treatment outcomes of patients infected with Enterococcus faecalis (n = 188) *.
Outcome
n (%) Unless Specified Otherwise		Ampicillin or Amoxicillin
(n = 67)		Vancomycin
(n = 33)		Nitrofurantoin
(n = 16)		Piperacillin/Tazobactam
(n = 21)		Ciprofloxacin
(n = 33)		Daptomycin
(n = 17)		p Value
Clinical cure51 (76.1)20 (60.6)14 (87.5)16 (76.2)29 (87.9)11 (64.7)0.064
Microbiological cure (n = 112)27 (69.2)12 (63.2)8 (88.9)13 (86.7)13 (81.3)10 (71.4)0.493
Duration of antibiotic therapy8 [6–8]8 [6–11]8 [6–15]6 [4–7.5]7 [5–8]7 [4–7.5]0.017
In-hospital mortality (n = 166)6 (10.7)8 (25)0 (0)6 (28.6)0 (0)6 (35.3)0.006
Length of stay (days); median [IQR] (n = 136)11 [5.5–16.5]20 [9–51]23 [1.5–41.5]12 [6–23]9.5 [3–19.6]14 [8.5–35]0.060
Recurrence (n = 185)31 (47.7)5 (15.2)4 (25)3 (14.3)10 (31.3)9 (52.9)0.005
Recurrence type 0.224
Relapse11 (35.5)4 (80)1 (25)1 (33.3)4 (40)1 (11.1)
Reinfection20 (64.5)1 (20)3 (75)2 (66.7)6 (60)8 (88.9)
IQR, interquartile range. * Of the 188 patients infected with E. faecalis, only one patient received linezolid, which was not included in the subgroup analysis.
Table 4. Treatment outcomes of patients infected with Enterococcus faecium (n = 92) *.
Table 4. Treatment outcomes of patients infected with Enterococcus faecium (n = 92) *.
Outcome
n (%) Unless Specified Otherwise		Ampicillin or Amoxicillin
(n = 3)		Vancomycin
(n = 29)		Linezolid
(n = 21)		Piperacillin/Tazobactam
(n = 5)		Ciprofloxacin
(n = 4)		Daptomycin
(n = 29)		p Value
Clinical cure3 (100)13 (44.8)15 (71.4)5 (100)4 (100)12 (41.4)0.012
Microbiological cure (n = 57)0 (0)10 (62.5)7 (53.8)2 (66.7)3 (100)9 (45)0.285
Duration of therapy6; 4–7 **7 [3.5–11]8 [7.5–11]8 [4.5–11.5]5.5; 5–7 **7 [5.5–10]0.093
In-hospital mortality (n = 91)0 (0)17 (58.6)5 (25)0 (0)0 (0)13 (44.8)0.019
Length of stay (days); median [IQR] (n = 82)0.5; 0–1 **23 [10.8–53.3]72 [34–123.5]16 [10–23.5]6; 6–15 **22 [7–47]<0.0001
Recurrence (n = 91)2 (66.7)10 (34.5)7 (33.3)1 (25)0 (0)6 (20.7)0.449
Recurrence type 0.238
Relapse0 (0)2 (20)2 (28.6)0 (0)0 (0)4 (66.7)
Reinfection2 (100)8 (80)5 (71.4)1 (100)0 (0)2 (33.3)
IQR, interquartile range. * Of the 92 patients infected with E. faecium, only one patient received nitrofurantoin, which was not included in the subgroup analysis. ** Due to the small sample size of inpatients, the median with the range is represented instead of the median [IQR].
Table 5. Evaluation of the association of different factors with clinical outcomes.
Table 5. Evaluation of the association of different factors with clinical outcomes.
FactorAdjusted Odds Ratio (95% Confidence Interval); p Value
Clinical CureMicrobiological CureIn-Hospital MortalityRecurrence
Age0.99 (0.97–1); 0.058NA1.03 (1.01–1.04); 0.007NA
Gender (female)NA0.34 (0.16–0.76); 0.008NA1.65 (0.82–3.34); 0.160
Location
OutpatientNANANANA
Non-ICU inpatientNA3.27 (1.18–9.08); 0.023NANA
ICUNA0.54 (0.08–3.47); 0.5175.55 (1.45–21.34); 0.013NA
UTI site NA NA
Upper/pyelonephritis 1.33 (0.67–2.64); 0.412-0.61 (0.26–1.43); 0.255-
Lower/cystitis Ref-Ref-
Species NA
Enterococcus faecalis1.52 (0.61–3.80); 0.9751.15 (0.38–3.52); 0.8080.45 (0.14–1.45); 0.181-
E. faeciumRefRefRef-
Liver disease0.45 (0.15–1.36); 0.1560.31 (0.08–1.15); 0.0802.75 (0.77–9.80); 0.120NA
HemodialysisNANA2.06 (0.71–6.00); 0.185NA
Recent antibiotic use1.44 (0.74–2.82); 0.289NANANA
Recent chemotherapy0.18 (0.07–0.52); 0.001NANANA
Having a risk factor for complicated UTI3.78 (1.33–10.77); 0.013NANANA
Antibiotic resistance
Ampicillin0.88 (0.35–2.20); 0.7800.31 (0.10–0.97); 0.0441.09 (0.36–3.26); 0.878NA
NitrofurantoinNANA1.02 (0.38–2.73); 0.964NA
Levofloxacin1.47 (0.69–3.15); 0.319NA0.68 (0.27–1.72); 0.410NA
Polymicrobial culture0.67 (0.32–1.37); 0.2660.43 (0.20–0.93); 0.0321.65 (0.80–3.43); 0.178NA
Other enterococcal culture0.41 (0.17–0.97); 0.042NANANA
Urinary catheter removedNANANA0.48 (0.24–0.98); 0.044
Antibiotic
Ampicillin or amoxicillinNANA0.53 (0.16–1.80); 0.3122.94 (1.40–6.17); 0.005
Vancomycin0.46 (0.22–0.98); 0.044NA3.40 (1.09–10.59); 0.035NA
NitrofurantoinNANA*NA
LinezolidNANA1.85 (0.68–5.06); 0.232NA
Piperacillin/tazobactamNANA2.62 (0.68–10.11); 0.162NA
Ciprofloxacin4.28 (1.18–15.56); 0.028NA*NA
Daptomycin0.57 (0.21–1.53); 0.268NA1.68 (0.45–6.20); 0.438NA
ICU, intensive care unit; NA, not applicable (not included in the multivariable regression analysis because the p value in the univariate analysis was >0.05); UTI, urinary tract infection. * Odds ratio could not be computed due to having a value of zero in the number of patients who died (i.e., none of the patients who received nitrofurantoin or ciprofloxacin died).
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MDPI and ACS Style

Thabit, A.K.; Al-Maqbali, J.S.; Alharthi, K.F.; Baotab, S.M.; Bankhar, A.M.; Wali, R.M.; Alzahrani, M.O.; Alharthi, A.K.; Alhamsaidi, T.M.; Al Busaidi, I.; et al. Antibiotic Outcomes of Enterococcal Urinary Tract Infections: A Retrospective Analysis from Saudi Arabia and Oman. Pathogens 2026, 15, 250. https://doi.org/10.3390/pathogens15030250

AMA Style

Thabit AK, Al-Maqbali JS, Alharthi KF, Baotab SM, Bankhar AM, Wali RM, Alzahrani MO, Alharthi AK, Alhamsaidi TM, Al Busaidi I, et al. Antibiotic Outcomes of Enterococcal Urinary Tract Infections: A Retrospective Analysis from Saudi Arabia and Oman. Pathogens. 2026; 15(3):250. https://doi.org/10.3390/pathogens15030250

Chicago/Turabian Style

Thabit, Abrar K., Juhaina S. Al-Maqbali, Khaled F. Alharthi, Salem M. Baotab, Abdullah M. Bankhar, Rayyan M. Wali, Mohammed O. Alzahrani, Asiya K. Alharthi, Taqwa M. Alhamsaidi, Ibrahim Al Busaidi, and et al. 2026. "Antibiotic Outcomes of Enterococcal Urinary Tract Infections: A Retrospective Analysis from Saudi Arabia and Oman" Pathogens 15, no. 3: 250. https://doi.org/10.3390/pathogens15030250

APA Style

Thabit, A. K., Al-Maqbali, J. S., Alharthi, K. F., Baotab, S. M., Bankhar, A. M., Wali, R. M., Alzahrani, M. O., Alharthi, A. K., Alhamsaidi, T. M., Al Busaidi, I., Mahrous, A. J., & Jose, J. (2026). Antibiotic Outcomes of Enterococcal Urinary Tract Infections: A Retrospective Analysis from Saudi Arabia and Oman. Pathogens, 15(3), 250. https://doi.org/10.3390/pathogens15030250

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