Enterococcal Urinary Tract Infections Research Articles

Linezolid in enterococcal urinary tract infection: a multicentre study.

Few data have been published on the efficacy of linezolid in enterococcal urinary tract infection (e-UTI). The aims of this study were to describe the characteristics of patients with enterococci UTI treated with linezolid, and to evaluate the efficacy and the tolerance of linezolid treatment. An observational multicentre retrospective study was conducted in 5 hospitals in France. Patients were included if they met the following criteria: ≥18 years, clinical and microbiological criteria for enterococcal UTI and linezolid treatment > 48h. Primary outcome was clinical failure. Eighty-one patients were included between January 2015 and December 2021. The median age was 73.0 [64; 83] years and 47 (58%) were men. The median Charlson comorbidity index was 3.00 [2; 6]. E. faecium was reported in 65 (80%) cases and E. faecalis in 26 cases (32%). Polymicrobial infections occurred in 41 (51%) cases. No enterococci was resistant to vancomycin. Before linezolid prescription an empiric antimicrobial treatment was started in 48 (59%) cases and was effective against enterococci in 19/48 (39.5%) patients for a median of 3.5 days [2.0; 4.0]. The median duration of linezolid antibiotic treatment was 13 days [10; 14]. Three adverse events were reported, none were serious but one led to discontinuation of treatment. Treatment failure was reported in 2 cases (2.5%). This study provides evidence for efficacy and safety of linezolid in enterococcal UTI.

Characteristics and outcomes of urinary tract infections caused by Enterococci: A multicenter retrospective study from two tertiary hospitals in Saudi Arabia

Enterococci are Gram-positive coccus bacteria that are normally present in the gastrointestinal tract and ordinarily function commensally with humans. Very few studies have investigated the characteristics of enterococcal infections. We aimed to characterize patients with urinary tract infections (UTIs) due to Enterococci and their outcomes. This was a retrospective cohort study between June 2012–November 2022. Patients who had clinically and microbiologically confirmed Enterococcal UTI based on a urine culture positive for E. faecalis or E. faecium with a count of ≥105 CFU/mL and having urinary tract symptoms were included. A total of 396 patients were eligible and included. The patients had a median age of 61 years and were mostly females (56.8 %). The most common characteristics were hospitalization in a non-ICU ward, having a urinary catheter, and recent use of antibiotics within the last 3 months (66.4 %, 59.3 %, and 51.8 %, respectively). Infection with E. faecalis was more common than E. faecium (77.3 % vs. 22.7 %). However, the latter exhibited higher rates of antibiotic resistance (P < 0.001 to several antibiotics) and was associated with significantly higher median C-reactive protein level (26.7 vs. 13 mg/dL; P = 0.025), mortality (23 % vs. 10.1 %; P = 0.002), and median length of stay (25 vs. 11.5 days; P < 0.001). We found that most patients with enterococcal UTIs had a history of having a urinary catheter and recent antibiotic use and were mostly females and hospitalized in non-ICU wards. E. faecium-infected patients experienced more severe episodes and poorer outcomes compared to patients infected with E. faecalis; thus, would need more aggressive therapy.

2842. Characteristics and Outcomes of Urinary Tract Infections (UTIs) Caused by Enterococci at a Tertiary Academic Medical Center in Saudi Arabia

Abstract Background Enterococci are Gram-positive coccus bacteria that are normally present in the gastrointestinal tract and ordinarily function commensally with humans. They are generally considered opportunistic and often associated with healthcare-associated infections. We aimed to characterize patients with UTIs due to Enterococci and their outcomes. Methods This was a retrospective cohort study between June 2012 and November 2022 of patients who had clinically and microbiologically confirmed Enterococcal UTI. Inclusion criteria included a urine culture positive for E. faecalis or E. faecium with a count of ≥ 105 CFU/mL and having urinary tract symptoms. Results Of 4,094 patients screened, 125 were eligible and included. Patients had a median age of 63.3 years and were mostly females (60%). The most common characteristics were having a catheter, hospitalization in a non-ICU ward, and recent use of antibiotics within 90 days. Infection with E. faecalis was more common than E. faecium (78.4% vs. 21.6%). However, the latter exhibited higher rates of antibiotic resistance (P &amp;lt; 0.001) and was associated with significantly higher median temperature (38 vs. 37.1°C; P &amp;lt; 0.001), mortality rates (24% vs. 6.9%; P = 0.020), and median length of stay (32 vs. 13 days; P &amp;lt; 0.001). Conclusion Most patients with enterococcal UTIs had a history of catheter and recent antibiotic use and were mostly females and hospitalized in non-ICU wards. Patients infected with E. faecium had more severe episodes compared with patients infected with E. faecalis. Therefore, patients infected with E. faecium should be followed more closely and have their antibiotics evaluated by infectious diseases experts of physicians and clinical pharmacists to potentially improve their outcomes. Disclosures All Authors: No reported disclosures

2205. Utilization of guiding comments imbedded within culture results to improve antimicrobial prescribing for enterococcal urinary tract infections in the ambulatory setting

Abstract Background Evaluate outcomes associated with utilizing guiding comments imbedded within the electronic health record’s (EHR) culture result to decrease the inappropriate use of cephalosporins in enterococcal urinary tract infections. Methods Data collected retrospectively from a regional health system from 02/01/22 to 02/28/23. Inclusion criteria was urine culture positive for enterococcus and active cephalosporin order. Exclusion criteria was cephalosporin treatment prescribed for a non-enterococcal organism and age less than 18 years. Patients were evaluated 6 months pre- and post-implementation of a microbiology comment added to streptococcus gamma and enterococcal cultures: “Enterococcus sp. are resistant to cephalosporins.” The primary outcome was rate of inappropriate prescribing of cephalosporins in enterococcal urinary tract infections in the ambulatory care setting. The secondary outcome was rate of 30-day follow-up visits required pre- and post-implementation of guiding comment. Follow-up was defined as either ambulatory visit, telephone visit, emergency department admission, or inpatient admission. Chi-Squared statistical test was utilized to compare nominal data. Results 93 patients were not included based on inclusion and exclusion criteria. 141 patients in the pre group and 146 patients in the post group were analyzed. After guiding comment implementation, the incidence of inappropriate treatment continuation decreased from 67.4% to 43.8% (RRR=35%, p=0.001). Follow up events included patient encounters related to urinary symptoms such as emergency department admissions, inpatient admission, ambulatory visits, and telephone encounters. Total patients requiring follow-up decreased from 44.7% (63/141) to 26.0% (38/146); 41.8% relative risk reduction (p = 0.001). Conclusion Providers assume enterococcus sensitivity to ampicillin equates to sensitivity to all beta-lactams. The implementation of guiding comments results significantly reduced the inappropriate use of cephalosporins to treat enterococcal urinary tract infections. Total follow-up visits were also significantly reduced which has the potential to improve patient experience. Enterococcal guiding comments should be implemented at heath care facilities when possible. Disclosures All Authors: No reported disclosures

Colonizer to Pathogen: A review on Enterococcal urinary tract infections

Abstract Enterococcus species has been historically known as part of the commensal flora of the normal human alimentary tract. Implicated in a wide array of illnesses encompassing bloodstream infections, urinary tract infections, wound infections as well as intra-abdominal infections, it has been rapidly emerging as a pathogen of interest owing to its propensity to acquire multidrug resistance. Due to the high antibiotic pressure in healthcare settings and salient intrinsic resistance to commonly used classes of antimicrobials, Enterococcus selectively proliferates in nosocomial settings. Their hardy nature and ability to resist a wide array of disinfectants enable them to proliferate on surfaces as well as provide for efficient transmission in hospital settings. Since Urinary tract infection (UTI) is one of the commonest infections caused by Enterococcus species. We attempt to comprehensively overview the paradigm shift of this erstwhile colonizer to one of the common uropathogen in hospital and community settings.

Prevalence of Enterococcal Urinary Tract Infections With Positive Nitrites in Urinalysis in Pediatric Patients With High-Risk for Enterococcal Infections.

Enterococcus is a relatively uncommon pathogen that causes urinary tract infections (UTIs) in healthy children. Most enterococcal infections occur in patients with risk factors such as anatomical or functional urinary tract anomalies, also known as CAKUT (congenital anomalies of kidney and urinary tract). Children who are suspected of having UTIs and who have certain risk factors are often treated specifically for enterococcal infection as part of their empiric regimen. Our primary objective was to determine the prevalence of enterococcal UTIs among high-risk children, and specifically among those with positive nitrite tests, with the goal of avoiding treatment with specific anti-enterococcal agents. This retrospective study included all the episodes of UTI treated at a tertiary pediatric center during 2010 to 2018. The data collected from medical records included nephrological and urological risk factors, nitrite status, and isolated pathogens. Of 931 episodes of UTI, 467 (50%) were considered high-risk. In all, 24 of the latter had Enterococcus as a single pathogen; 23 (96%) of these occurred in patients with negative nitrites in the first urine dipstick taken. The sole patient with high-risk factors, a positive nitrite test and coexisting enterococcal UTI had a history of previous enterococcal UTIs. In pediatric patients with nephrological and urological risk factors, who have positive nitrites in urinalysis, the risk for enterococcal UTI appears substantially low. Therefore, in this context, specific anti-enterococcal empirical antibiotic therapy may be unnecessary.

Enterococcal Urinary Tract Infections: A Review of the Pathogenicity, Epidemiology, and Treatment.

Urinary tract infections (UTIs) are among the most common causes of infections worldwide and can be caused by numerous uropathogens. Enterococci are Gram-positive, facultative anaerobic commensal organisms of the gastrointestinal tract that are known uropathogens. Enterococcus spp. has become a leading cause of healthcare associated infections, ranging from endocarditis to UTIs. In recent years, there has been an increase in multidrug resistance due to antibiotic misuse, especially in enterococci. Additionally, infections due to enterococci pose a unique challenge due to their ability to survive in extreme environments, intrinsic antimicrobial resistance, and genomic malleability. Overall, this review aims to highlight the pathogenicity, epidemiology, and treatment recommendations (according to the most recent guidelines) of enterococci.

MP34-14 MEDICATIONS MOSTLY ASSOCIATED WITH URINARY TRACT INFECTIONS (UTIS): ASSESSMENT OF THE EUDRAVIGILANCE (EV) AND FOOD AND DRUG ADMINISTRATION (FDA) PHARMACOVIGILANCE DATABASES ENTRIES

MP34-14 MEDICATIONS MOSTLY ASSOCIATED WITH URINARY TRACT INFECTIONS (UTIS): ASSESSMENT OF THE EUDRAVIGILANCE (EV) AND FOOD AND DRUG ADMINISTRATION (FDA) PHARMACOVIGILANCE DATABASES ENTRIES

Aminopenicillins vs non-aminopenicillins for treatment of enterococcal lower urinary tract infections

Aminopenicillins (APs) achieve urinary concentrations that exceed typical minimum inhibitory concentrations for enterococcal lower urinary tract infection (UTI). The local clinical microbiology laboratory discontinued routine susceptibilities on enterococcal urine isolates, and reports that 'APs are predictably reliable for uncomplicated enterococcal UTI'. The objective of this study was to compare outcomes of APs with non-APs (NAPs) for enterococcal lower UTIs. This was an institutional-review-board-approved, retrospective cohort of adults hospitalized with symptomatic enterococcal lower UTIs from 2013 to 2021. The primary endpoint was composite clinical success at 14 days, defined as resolution of symptoms without new symptoms and no repeat culture growth of the index organism. A non-inferiority analysis was utilized with a 15% margin, and logistic regression evaluated characteristics associated with 14-day failure. In total, 178 subjects were included: 89 AP patients and 89 NAP patients. Vancomycin-resistant enterococci (VRE) were identified in 73 (82%) AP patients and 76 (85%) NAP patients (P=0.54); in total, 34 (38.2%) AP patients and 66 (74.2%) NAP patients had confirmed Enterococcus faecium (P<0.001). Amoxicillin (n=36, 40.5%) and ampicillin (n=36, 40.5%) were the most commonly used APs, and linezolid (n=41, 46%) and fosfomycin (n=30, 34%) were the most commonly used NAPs. Fourteen-day clinical success rates for APs and NAPs were 83.1% and 82.0%, respectively [1.1% difference, 97.5% confidence interval (CI) -0.117 to 0.139]. Among the E. faecium subgroup, 14-day clinical success was observed in 27/34 (79.4%) AP patients and 53/66 (80.3%) NAP patients (P=0.916). On logistic regression, APs were not associated with 14-day clinical failure (adjusted odds ratio 0.84, 95% CI 0.38-1.86). APs were non-inferior to NAPs for treating enterococcal lower UTIs, and may be considered irrespective of susceptibility results.

Vancomycin Resistant Enterococcal Urinary Tract Infection: A Potential Threat

Introduction: Enterococci are considered less virulent organisms, but have incurred recognition for being notorious for their acquisition and transfer of resistance. The greatest potential threat posed by enterococci is vancomycin resistance. The transfer of enterococcal vancomycin resistance to Staphylococcus aureus has been achieved making scientists apprehensive of its consequences. Aim: To find the prevalence of Vancomycin-Resistant Enterococci (VRE) and to determine the antimicrobial resistance pattern in enterococcal urinary isolates. Materials and Methods: A cross-sectional study was carried out on all urinary samples suspected of Urinary Tract Infection (UTI) received for duration of one year from April 2021 to March 2022 in the Department of Microbiology at Uttar Pradesh University of Medical Sciences, Saifai, Etawah, Uttar Pradesh. Enterococci were isolated and identified with a VITEK-2® COMPACT (bioMérieux) automated system. The antibiotic susceptibility pattern was determined by Kirby-Bauer disc diffusion method. Further, confirmation of VRE was done by Minimum Inhibitory Concentration (MIC) E-test. Results: A total of 128 urinary enterococcal isolates were identified with the male-to-female ratio 1.37:1 and mean age of patients was 37.18±22.64 years. Out of total, 71.87% were identified as Enterococcus faecalis followed by 24.21% Enterococcus faecium and the rare species (4%) including E.durans, E.hirae, E.raffinosus. The prevalence of VRE was found to be 8.6%. Maximum resistance by isolates has been shown against ampicillin, erythromycin, ciprofloxacin, and doxycycline. All isolates were sensitive to linezolid. Nitrofurantoin resistance was observed in 4.34% and 25.80% of E.faecalis and E.faecium isolates respectively. Conclusion: In this study, it was revealed that the emergence of VRE in urinary isolates with antimicrobial resistance was higher among E. faecium. All this puts pressure on strict compliance with a multidimensional approach with collaboration of antibiotic stewardship, educational and surveillance programs.

2224. Aminopenicillins versus Non-aminopenicillins for Treatment of Enterococcal Cystitis

Abstract Background Aminopenicillins achieve urinary concentrations that overcome aminopenicillin resistance in Enterococcus spp. lower urinary tract infections (UTI). With this rationale, our clinical microbiology laboratory discontinued routine identification on Enterococcus urine isolates in 2012 and report “aminopenicillins are predictably reliable for uncomplicated enterococcal UTI”. The study objective was to compare outcomes of patients treated with aminopenicillins (AP) versus non-aminopenicillins (NAP) for enterococcal cystitis. Methods IRB approved, retrospective cohort of adults hospitalized with symptomatic enterococcal cystitis from 2013-2021. Exclusion: definitive E. faecalis, enterococcal UTI in past year, review of systems unavailable/altered mental status, urinary instrumentation except for stent/catheter, systemic infection, fever, genitourinary trauma, renal transplant. Primary endpoint: clinical and microbiologic success at 14 days, defined as resolution of symptoms without new symptoms and no repeat culture growth of index organism. Logistic regression evaluated characteristics associated with 14-day failure. Sample size of 178 calculated for non-inferiority using α=0.025, β=0.8, 15% non-inferiority margin. Results 178 subjects included, 89 AP, 89 NAP . VRE identified: 73 (82%) AP and 76 (85%) NAP (P=0.50). Amoxicillin (36/89, 40%) and ampicillin (36/89, 40%) used most in AP. Linezolid (41, 46%) and fosfomycin (30, 34%) most common agents in NAP. 14-day clinical composite endpoint was no different between AP and NAP groups, respectively (74 [83%] vs. 73 [82%], P=0.84). No variables independently predicted failure (Table 1). Non-inferiority analysis for AP vs. NAP for 14-day composite: mean difference 1.1% (-0.14 to 0.127, 97.5% CI; P=0.42). Definite E. faecium subgroup: 14-day clinical composite success for was no different between AP and NAP groups, respectively (27/34 [79%] vs. 53/66 [80%], P=0.916). Conclusion AP were non-inferior to NAP, supporting their use as first-line therapy for cystitis due to enterococci, including E. faecium. This stewardship strategy has implications to preserve VRE active therapies (e.g. linezolid) for serious infections. Disclosures All Authors: No reported disclosures.

Aminopenicillins for treatment of ampicillin-resistant enterococcal urinary tract infections.

The purpose of this review is to describe the theory behind and data supporting use of aminopenicillins in the treatment of ampicillin-resistant enterococcal urinary tract infections. Aminopenicillin concentrations in the urine may be high enough to achieve bacterial eradication and clinical cure for infections affecting the lower genitourinary tract, even in the context of in vitro resistance based on established susceptibility breakpoints. A literature search was conducted to identify original research articles describing the use of aminopenicillins in the treatment of urinary tract infections caused by ampicillin-resistant Enterococcus species. Three published retrospective cohort studies were identified, all of which reported that aminopenicillins had similar rates of clinical cure as other antibiotic classes prescribed for the treatment of enterococcal urinary tract infections. Both pharmacokinetic/pharmacodynamic principles and limited retrospective clinical data support the use of aminopenicillins in the treatment of lower urinary tract infections caused by Enterococcus species, even when the isolates have a minimum inhibitory concentration that exceeds the susceptibility breakpoint.

Characterization and Comparison of Enterococcus spp. Isolates from Feces of Healthy Dogs and Urine of Dogs with UTIs.

Simple SummaryInfections caused by Enterococcus spp. represent a serious threat to human and animal health due to difficulties in treatment. Indeed, these bacteria are a very able “trafficker” of antimicrobial resistance genes and for this reason they are often resistant to many antimicrobials. In this study we explored the role of pet dogs as possible carriers and targets of antimicrobial resistant and virulent enterococci. Isolates collected from feces of healthy animals and urine of dogs suffering with UTIs were characterized and compared. Strains resulted as resistant to many of the antimicrobials tested and almost of them were multidrug-resistant. Diffuse resistance was recorded for compounds routinely employed in human and pet therapy. Genes responsible for antimicrobial resistance were widely detected. E. faecalis and E. faecium resulted as equally distributed in stool samples, while E. faecalis prevailed among UTI isolates; virulence genes were more often detected in bacteria belonging to this species. Our data confirm that enterococci inhabitant of the gut flora probably represent the main source of UTI in dogs. Furthermore, healthy and sick pet dogs could be spreaders of antimicrobial and virulent enterococci, representing a possible hazard for other animals and owners.Enterococcus spp. are opportunistic pathogens of both humans and animals characterized by high resistance to antimicrobials. Dogs could be intestinal carriers or suffer from Enterococcus infections, mainly urinary tract infections (UTIs). This study aimed to analyze and compare Enterococcus spp. isolated from healthy dog stools and sick dog urine. Overall, 51 isolates (29 from stools and 22 from UTI) were characterized at species level and tested for antimicrobial resistance, biofilm production and presence of resistance and virulence genes. E. faecium and E. faecalis resulted as equally distributed in stools samples, while E. faecalis predominated among UTI isolates. HLAR phenotype was detected in 47.1% isolates; 64.7% isolates were resistant to ampicillin (47.1% with a MIC ≥ 64 µg/mL). High levels of resistance were recorded for fluoroquinolones (enrofloxacin 74.5%, ciprofloxacin 66.7%), clindamycin (84.3%), tetracycline (78.4%) and quinupristin–dalfopristin (78.4%). No vancomycin resistant strains were detected. All but one isolate were multidrug-resistant. Most detected resistance genes were tetM (70.5%), pbp4 (52.9%) and aph(3′)-IIIa (39.2%). All isolates were able to produce biofilm, but isolates from UTIs and belonging to E. faecalis more frequently resulted in strong biofilm producers. Most detected virulence genes were asa1 (52.9%), gelE (41.2%), cylA (37.3%) and esp (35.3%); all of them resulted as more frequently associated to E. faecalis. No particular differences emerged between isolates from feces and UTI, considering all evaluated aspects. Our results confirm pet dogs as carriers of multidrug-resistant enterococci; stool microflora could be considered as the most probable source of enterococcal UTI and E. faecalis carried by dogs seems to be more virulent than E. faecium, justifying its more frequent involvement in urinary tract infections.

Risk factors for enterococcal urinary tract infections: a multinational, retrospective cohort study.

Complicated urinary tract infection (cUTI) is a frequent cause of morbidity. In this multinational retrospective cohort study, we aimed to demonstrate risk factors for enterococcal UTI. Univariate and multivariate analyses of risk factors for enterococcal infection were performed. Among 791 hospitalized patients with cUTI, enterococci accounted for approximately 10% of cases (78/791). Risk factors for enterococcal UTI in multivariable analysis were male gender, age range of 55-75 years, catheter-associated UTI, and urinary retention. This information may assist treating physicians in their decision-making on prescribing empiric anti-enterococcus treatment to hospitalized patients presenting with cUTI and thus improve clinical outcomes.

Enterococcal Urinary Tract Infection in Newborns at a Pediatric Hospital in Saudi Arabia

The main goal of this study was to examine the spectrum of Enterococci that cause urinary tract infection in newborns. This study was conducted during September 2018 to November 2018 at Prince Sattam Bin Abdul Aziz University. A total of 317 urine samples were taken from newborns admitted to the Children's Hospital in the city of Riyadh, Kingdom of Saudi Arabia. In total, 30 (9.5%) Enterococcal strains were isolated from 317 samples. Of these, 17 (56.6%) were from male and 13 (43.4%) were from female patients. From antibiotic sensitivity assay, it was observed that all of the isolates were resistant to clindamycin. But Imipenem and Augmentin were found highly sensitive. So, these sensitive antibiotics can be used for the treatment of newborns UTIs caused by the enterococcal strains.&#x0D; Dhaka Univ. J. Pharm. Sci. 19(2): 119-124, 2020 (December)

Characterization of enterococcal urinary tract infections, with special reference to High Level Aminoglycoside Resistance (HLGR)

Background: Multidrug-resistant Enterococci are major problem and are increasingly reported worldwide. Enterococci have converted over the years from a normal gut commensal to opportunistic nosocomial as well as community acquired pathogen. High level resistance to Aminoglycosides and concomitant resistance to Vancomycin reduces the treatment options and complicated the management of serious infections caused by Enterococci. Methods and materials: A retrospective analysis was conducted in the Department of Microbiology, SGPGI for a period of 10 months from Jan 2018 to October 2018. Enterococcus isolated from urine colony counts of ≥10 5 colony-forming units per ml (CFU/ml) were included in the study. Identification was performed by MALDI TOF and Antimicrobial susceptibility testing was performed by the VITEK 2.0 in accordance to CLSI guidelines. Results: In the study, 186 Enterococci spp. were isolated out of which 159/186 (85.48%) were E.faecalis and 27/186 (14.51%) were E.faecium. High Level Aminoglycoside resistance (HLG) was seen in 67/186 (36.02%) of which E.faecalis comprised of 43/67 (64.17%). Three isolates, all identified as E. faecium, were found to be resistant to High level Gentamycin and Vancomycin. Overall, antibiogram of the isolates showed a high resistance to ampicillin, followed by ciprofloxacin, High level Gentamycin (36.02%), High level Streptomycin (36.02%), vancomycin (1.61%), teicoplanin (1.61%), linezolid (1.61%) and nitrofurantoin (1%). A subset of E.faecalis were randomly selected and characterised for HLG resistance genes. DISCUSSION-History of recent hospitalization and the presence of indwelling urinary catheter was associated with VRE and HLGR enterococci infection or colonization. Overall, High-Level Aminoglycoside Resistance (HLAR) was observed more than glycopeptide resistance. Isolates resistant to HLG but susceptible to vancomycin expressed more virulence factors. Conclusion: This study highlights the temporal increase in antimicrobial resistance and in MDR bacteria causing UTI creates important therapeutic limitations. Surveillance strategies need to be upgraded and implemented in order to prevent the emergence and further spread of not only VRE but also HLAR enterococci in the hospital.

Oral Fosfomycin Treatment for Enterococcal Urinary Tract Infections in a Dynamic In Vitro Model.

There are limited treatment options for enterococcal urinary tract infections, especially vancomycin-resistant Enterococcus (VRE). Oral fosfomycin is a potential option, although limited data are available guiding dosing and susceptibility. We undertook pharmacodynamic profiling of fosfomycin against E. faecalis and E. faecium isolates using a dynamic in vitro bladder infection model. Eighty-four isolates underwent fosfomycin agar dilution susceptibility testing (E. faecalis MIC50/90 32/64 μg/ml; E. faecium MIC50/90 64/128 μg/ml). Sixteen isolates (including E. faecalis ATCC 29212 and E. faecium ATCC 35667) were chosen to reflect the MIC range and tested in the bladder infection model with synthetic human urine (SHU). Under drug-free conditions, E. faecium demonstrated greater growth restriction in SHU compared to E. faecalis (E. faecium maximal growth 5.8 ± 0.6 log10 CFU/ml; E. faecalis 8.0 ± 1.0 log10 CFU/ml). Isolates were exposed to high and low fosfomycin urinary concentrations after a single dose, and after two doses given over two days with low urinary concentration exposure. Simulated concentrations closely matched the target (bias 2.3%). E. faecalis isolates required greater fosfomycin exposure for 3 log10 kill from the starting inoculum compared with E. faecium The ƒAUC0-72/MIC and ƒ%T > MIC0-72 for E. faecalis were 672 and 70%, compared to 216 and 51% for E. faecium, respectively. There was no rise in fosfomycin MIC postexposure. Two doses of fosfomycin with low urinary concentrations resulted in equivalent growth inhibition to a single dose with high urinary concentrations. With this urinary exposure, fosfomycin was effective in promoting suppression of regrowth (>3 log10 kill) in the majority of isolates.

Should the Absence of Urinary Nitrite Influence Empiric Antibiotics for Urinary Tract Infection in Young Children?

Screening for urinary tract infection (UTI) includes urinary nitrite testing by dipstick urinalysis. Gram-negative enteric organisms produce urinary nitrite and represent the most common uropathogens. Enterococcus, a less common uropathogen, does not produce nitrite and has a unique antibiotic resistance pattern. Whether to adjust empiric antibiotics in the absence of urinary nitrite has not been established. Our primary objective was to determine prevalence of enterococcal UTI among young children with a nitrite negative urinalysis. A retrospective study of children aged less than 2 years evaluated in the emergency department for possible UTI and had a paired urinalysis and urine culture was performed. Urinary tract infection was defined by catheterized culture yielding greater than or equal to 50,000 colony-forming units per milliliter of a single uropathogen. Prevalence of uropathogens among nitrite negative samples was studied. A total of 7599 children were studied. Median (interquartile range) age was 5.6 (2.3-11.2) months, and 57% were female. Prevalence of UTI was 8.1%. Enterococcus was the uropathogen in 2.1% of UTIs, and all cases had negative dipstick nitrite. Among nitrite negative UTIs, 95.6% of uropathogens were gram-negative and only 3.2% (confidence interval, 1.8%-5.3%) were enterococcus. None of the 200 UTIs with positive nitrite yielded enterococcus (upper confidence interval, 1.4%). Among children with positive leukocyte esterase and negative nitrite, only 0.7% of cases had enterococcal UTI. Only 3% of nitrite negative UTIs were caused by enterococcus. Given the low prevalence of enterococcal UTI, the absence of dipstick nitrite should not affect routine empiric antibiotic choice for presumptive UTI in young children.

Revisiting Nitrofurantoin for Vancomycin Resistant Enterococci.

Enterococcal infection has emerged as a major therapeutic challenge. Emergence of High Level Aminoglycoside Resistance (HLAR) and Vancomycin-Resistant Enterococcus (VRE) has further limited the drug therapy in enterococcal infections. However, nitrofuratoin being an old drug reported to have less resistance in comparison to the other classes of antimicrobial agents. To detect susceptibility of nitrofurantoin against VRE isolates from Urinary Tract Infection (UTI) of outdoor and indoor patient departments. An observational study was carried out at a tertiary care hospital in New Delhi over a period of six months (from November 2015 to April 2016). A total of 14,714 urine samples were collected and processed from the patients symptomatic for UTI. The enterococcal isolates were identified and confirmed by standard phenotypic tests. The antimicrobial susceptibility tests of isolated organisms were performed by Kirby-Bauer Disc Diffusion Method as per Clinical and Laboratory Standards Institute (CLSI) 2015 guidelines. The Wilcoxon rank-sum (Mann-Whitney) test was used to compare continuous variables. Chi-square or Fisher's exact tests were used to compare categorical variables. p<0.05 was considered as significant. A total of 70 enterococci species {Enterococcus faecalis (n=9), Enterococcus faecium, (n=61)} were isolated. Twenty six out of 70 isolates were observed resistant to vancomycin. Among 26 VRE, 21(80.76%) were susceptible to nitrofurantoin. Both the species {E. faecalis (80.32%) and E. faecium (88.8%)} were uniformly susceptible to nitrofurantoin. Nitrofurantoin has retained antimicrobial efficacy against emerging VRE in vitro and can be used for treatment of enterococcal urinary tract infections.

Enterococcal urinary tract infections analyzed at “Cantacuzino” National Research Institute

Enterococcal urinary tract infections analyzed at “Cantacuzino” National Research Institute