Antibiotic treatment failure of uncomplicated urinary tract infections in primary care.

BACKGROUND: Higher resistance rates of > 20% have been noted in Enterobacteriaceae urinary isolates towards ciprofloxacin and co-trimoxazole (C + C) in Singapore, compared with amoxicillin-clavulanate and nitrofurantoin (AC + N). This study examined if treatment failure varied between different antibiotics, given different resistant rates, for uncomplicated urinary tract infections (UTIs) managed in primary care. We also aimed to identify gaps for improvement in diagnosis, investigations, and management. METHODS: A retrospective cohort study was conducted from 2019 to 2021 on female patients aged 18-50 with uncomplicated UTIs at 6 primary care clinics in Singapore. ORENUC classification was used to exclude complicated UTIs. Patients with uncomplicated UTIs empirically treated with amoxicillin-clavulanate, nitrofurantoin, ciprofloxacin or co-trimoxazole were followed-up for 28 days. Treatment failure was defined as re-attendance for symptoms and antibiotic re-prescription, or hospitalisation for UTI complications. After 2:1 propensity score matching in each group, modified Poisson regression and Cox proportional hazard regression accounting for matched data were used to determine risk and time to treatment failure. RESULTS: 3194 of 4253 (75.1%) UTIs seen were uncomplicated, of which only 26% were diagnosed clinically. Urine cultures were conducted for 1094 (34.3%) uncomplicated UTIs, of which only 410 (37.5%) had bacterial growth. The most common organism found to cause uncomplicated UTIs was Escherichia coli (64.6%), with 92.6% and 99.4% of isolates sensitive to amoxicillin-clavulanate and nitrofurantoin respectively. Treatment failure occurred in 146 patients (4.57%). Among 1894 patients treated with AC + N matched to 947 patients treated with C + C, patients treated with C + C were 50% more likely to fail treatment (RR 1.49, 95% CI 1.10-2.01), with significantly higher risk of experiencing shorter time to failure (HR 1.61, 95% CI 1.12-2.33), compared to patients treated with AC + N. CONCLUSION: Treatment failure rate was lower for antibiotics with lower reported resistance rates (AC + N). We recommend treating uncomplicated UTIs in Singapore with amoxicillin-clavulanate or nitrofurantoin, based on current local antibiograms. Diagnosis, investigations and management of UTIs remained sub-optimal. Future studies should be based on updating antibiograms, highlighting its importance in guideline development.

Nomenclature, diagnosis and management of drug-induced autoimmune-like hepatitis (DI-ALH): An expert opinion meeting report.

Drug-induced liver injury (DILI) can mimic almost all other liver disorders. A phenotype increasingly ascribed to drugs is autoimmune-like hepatitis (ALH). This article summarises the major topics discussed at a joint International Conference held between the Drug-Induced Liver Injury consortium and the International Autoimmune Hepatitis Group. DI-ALH is a liver injury with laboratory and/or histological features that may be indistinguishable from those of autoimmune hepatitis (AIH). Previous studies have revealed that patients with DI-ALH and those with idiopathic AIH have very similar clinical, biochemical, immunological and histological features. Differentiating DI-ALH from AIH is important as patients with DI-ALH rarely require long-term immunosuppression and the condition often resolves spontaneously after withdrawal of the implicated drug, whereas patients with AIH mostly require long-term immunosuppression. Therefore, revision of the diagnosis on long-term follow-up may be necessary in some cases. More than 40 different drugs including nitrofurantoin, methyldopa, hydralazine, minocycline, infliximab, herbal and dietary supplements (such as Khat and Tinospora cordifolia) have been implicated in DI-ALH. Understanding of DI-ALH is limited by the lack of specific markers of the disease that could allow for a precise diagnosis, while there is similarly no single feature which is diagnostic of AIH. We propose a management algorithm for patients with liver injury and an autoimmune phenotype. There is an urgent need to prospectively evaluate patients with DI-ALH systematically to enable definitive characterisation of this condition.

A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry.

BACKGROUND & AIMS: No multi-national prospective study of drug-induced liver injury (DILI) has originated in Europe. The design of a prospective European DILI registry, clinical features and short-term outcomes of the cases and controls is reported. METHODS: Patients with suspected DILI were prospectively enrolled in the United Kingdom, Spain, Germany, Switzerland, Portugal and Iceland, 2016-2021. DILI cases or non-DILI acute liver injury controls following causality assessment were enrolled. RESULTS: Of 446 adjudicated patients, 246 DILI patients and 100 had acute liver injury due to other aetiologies, mostly autoimmune hepatitis (n = 42) and viral hepatitis (n = 34). DILI patients (mean age 56 years), 57% women, 60% with jaundice and 3.6% had pre-existing liver disease. DILI cases and non-DILI acute liver injury controls had similar demographics, clinical features and outcomes. A single agent was implicated in 199 (81%) DILI cases. Amoxicillin-clavulanate, flucloxacillin, atorvastatin, nivolumab/ipilimumab, infliximab and nitrofurantoin were the most commonly implicated drugs. Multiple conventional medications were implicated in 37 (15%) and 18 cases were caused by herbal and dietary supplements. The most common single causative drug classes were antibacterials (40%) and antineoplastic/immunomodulating agents (27%). Overall, 13 (5.3%) had drug-induced autoimmune-like hepatitis due to nitrofurantoin, methyldopa, infliximab, methylprednisolone and minocycline. Only six (2.4%) DILI patients died (50% had liver-related death), and another six received liver transplantation. CONCLUSIONS: In this first multi-national European prospective DILI Registry study, antibacterials were the most commonly implicated medications, whereas antineoplastic and immunomodulating agents accounted for higher proportion of DILI than previously described. This European initiative provides an important opportunity to advance the study on DILI.

Anthocran® Phytosome®: Prevention of Recurring Urinary Infections and Symptoms after Catheterization.

In this preliminary pilot registry study, we investigated the effects of the oral supplementation of a standardized cranberry extract (Anthocran® Phytosome®, Indena) delivered by a lecithin-based system, for the prophylactic management of recurrent-urinary tract infections (R-UTIs). We included 64 otherwise healthy subjects who underwent a surgical procedure and required post-surgical urinary catheterization for high-risk UTIs or a previous history of R-UTIs. Patients were given supplementation with the standardized cranberry extract at the dose of either 120 mg/day (n = 12) or 240 mg/day (n = 12) or assigned to a control group consisting of standard management (SM; n = 18) or nitrofurantoin administration (n = 22) for 4 weeks. After 4 weeks, patients receiving the standardized cranberry supplementation reported to have a more effective reduction in UTI symptoms, as assessed on the visual analogue scale, compared with patients in the SM or nitrofurantoin groups. The occurrence of hematuria and urine bacterial contamination were decreased among patients treated with the supplement compared with controls (p < 0.05). The cranberry extract was also superior to the control management in terms of recurrence of signs/symptoms, with none of the patients in this group suffering from a R-UTI in the 3 months following the study end (p < 0.05). The supplementation showed an optimal safety profile, with no significant adverse events and no drop-outs in the supplement group. This registry shows that this cranberry extract is effective as a supplementary, preventive management in preventing post-operative, post-catheter UTIs; the product has a good tolerability profile.

Treating urinary tract infections in public sector primary healthcare facilities in Cape Town, South Africa: A pharmaceutical perspective.

BACKGROUND: Antibiotic resistance is a global healthcare burden complicating the management of infections. Urinary tract infections (UTIs) are commonly treated in primary care. Managing UTIs appropriately in primary care can combat antibiotic resistance. The treatment practices for UTIs in primary care in Western Cape Province, South Africa, are not well described. OBJECTIVES: To describe treatment of UTIs in adults in primary care in the Cape Town metropole public sector of the Western Cape. METHODS: A retrospective multicentre medical records review of patients diagnosed with UTIs was conducted during 1 October 2020 - 28 February 2021. Six public sector primary healthcare facilities were included in the study through random selection from three of the four substructures in the Cape Town metropole. Medical records of adult patients diagnosed with UTIs, through clinical diagnosis or microbiological testing, were identified via a selective sampling process. Data were collected from medical records using a standardised data collection tool. RESULTS: A total of 401 UTI episodes occurred in 383 patients during the study period. The majority of UTI episodes (84.3%) occurred in females, complicated UTIs (74.1%) were more common than uncomplicated UTIs, and nitrofurantoin (57.1%) was frequently prescribed, followed by ciprofloxacin (39.7%). Compliance with urine microscopy recommendations was low (6.7%), and antibiotics were appropriately selected in 75.0% of uncomplicated and 70.0% of complicated UTI episodes. CONCLUSION: Interventions are required to improve compliance with treatment recommendations as per the standard treatment guidelines, especially when selecting the appropriate antibiotic, duration of therapy and urine microscopy.

Zinc Oxide/Phosphorus-Doped Carbon Nitride Composite as Potential Scaffold for Electrochemical Detection of Nitrofurantoin.

Herein, we present an electrocatalyst constructed by zinc oxide hexagonal prisms/phosphorus-doped carbon nitride wrinkles (ZnO HPs/P-CN) prepared via a facile sonochemical method towards the detection of nitrofurantoin (NF). The ZnO HPs/P-CN-sensing platform showed amplified response and low-peak potential compared with other electrodes. The exceptional electrochemical performance could be credited to ideal architecture, rapid electron/charge transfer, good conductivity, and abundant active sites in the ZnO HPs/P-CN composite. Resulting from these merits, the ZnO HPs/P-CN-modified electrode delivered rapid response (2 s), a low detection limit (2 nM), good linear range (0.01-111 µM), high sensitivity (4.62 µA µM-1 cm2), better selectivity, decent stability (±97.6%), and reproducibility towards electrochemical detection of NF. We further demonstrated the feasibility of the proposed ZnO HPs/P-CN sensor for detecting NF in samples of water and human urine. All the above features make our proposed ZnO HPs/P-CN sensor a most promising probe for detecting NF in natural samples.

Assessment of nationally recommended antibiotics for treatment of UTI in U.S.-Mexico border emergency departments.

BACKGROUND: Urinary tract infections (UTIs) seen in the emergency department are commonly treated as an outpatient with oral antibiotics. Given that antibiotics are available for over-the-counter purchase in Mexico, there is speculation that potential misuse and overuse of antibiotics in United States-Mexico border areas could lead to antibiotic resistance patterns that would render some empiric treatments for UTIs less effective. The purpose of this study was to examine the effectiveness of Infectious Disease Society of America (IDSA) guideline-recommended antibiotics for treatment of outpatient UTI diagnosed in the emergency department. Data were collected from a county hospital on the U.S.-Mexico border with a metropolitan area of over 2 million people. Secondary analysis included frequency of urine culture isolated, resistance rates of urine pathogens, and prescriber habits. METHODS: This study was a retrospective chart review of adult patients diagnosed and treated for UTI from August 1, 2019, to February 29, 2020. Culture results of included patients were analyzed against in vitro-tested antibiotics. Bacterial isolate frequency, resistance rates, and prescribing habits were collected. RESULTS: A total of 985 patient charts were reviewed, of which 520 patients met inclusion criteria for analysis of prescribing habits. Of these, 329 positive bacterial culture growths were included in the analysis of antibiotic resistance rates. Oral antibiotics with comparatively lower resistance rates were amoxicillin/clavulanate, cefdinir, cefuroxime, and nitrofurantoin. Oral antibiotics with notably high resistance rates included trimethoprim-sulfamethoxazole (TMP-SMX), tetracycline, ciprofloxacin, levofloxacin, and cephalexin. Nitrofurantoin was prescribed most frequently for outpatient treatment of UTI/cystitis (41.6%) while cephalexin was the most commonly prescribed antibiotic for outpatient treatment of pyelonephritis (50%). CONCLUSION: Our findings suggest that, while part of standard IDSA guidelines, fluoroquinolones and TMP-SMX are not ideal empiric antibiotics for treatment of outpatient UTI in the U.S.-Mexico border region studied due to high resistance rates. Although not listed as first line agents per current IDSA recommendations, 2nd and 3rd generation cephalosporins, and amoxicillin/clavulanate would be acceptable options given resistance patterns demonstrated in accordance with IDSA allowance for tailoring selection to local resistance. Nitrofurantoin appears to be consistent with recommendations and demonstrates a favorable resistance profile for treatment of outpatient UTI within this region.

Urinary Tract Infections in Long-term Care: Evaluation of Uropathogens, Antibiotic Susceptibility, and Empiric Treatment.

Objective To devise a residential empiric treatment algorithm, describe common uropathogens associated with urinary tract infections (UTIs) in residential care, assess all-pathogen and non-ESBL (extended-spectrum beta-lactamase) Escherichia coli antibiotic susceptibilities, and report the percentage of antibiotic use. Design A retrospective chart review of 198 residents with positive urine cultures from September 2019 to September 2020. Setting Institutional long-term care facility. Participants The exclusion criteria were negative urine culture, mixed organisms on urine culture, no antibiotic treatment, signs and symptoms of systemic infection, hospitalization because of systemic infection, and intravenous antibiotic treatment. The entire population was screened. Results The most prevalent pathogens were non-ESBL E. coli (29%), Proteus mirabilis (12%), Klebsiella pneumoniae (8%), and ESBL E. coli (8%). All-pathogen susceptibilities were 79.6% (amoxicillin/clavulanate), 64.1% (nitrofurantoin), 50.5% (sulfamethoxazole/trimethoprim), 43.7% (cephalexin), 42.7% (amoxicillin), and 41.8% (ciprofloxacin). Amoxicillin/clavulanate (96.7%), nitrofurantoin (90.0%) and sulfamethoxazole/trimethoprim (83.3%) demonstrated the highest non-ESBL E. coli susceptibilities. Nitrofurantoin was the most prescribed antibiotic (21%), followed by amoxicillin/clavulanate (19%) and ciprofloxacin (17%). Conclusion Based on the data, amoxicillin/clavulanate and nitrofurantoin are appropriate first-line options for empiric treatment of symptomatic cystitis in this long-term care facility, with sulfamethoxazole/trimethoprim as an alternative. Ciprofloxacin was overprescribed despite its low susceptibilities to commonly encountered pathogens, which emphasizes the need for a UTI empiric treatment algorithm tailored towards residential care.

Susceptibility to first choice antimicrobial treatment for urinary tract infections to Escherichia coli isolates from women urine samples in community South Brazil.

E. coli is the main pathogen of UTI. It is important to be aware the local epidemiological data for an appropriate initial treatment. Resistance to antimicrobial agents has increased, especially to first-choice antibiotics in the treatment of cystitis. There are few studies on the sensivity profile of community uropathogen in our region. OBJECTIVE: To characterize antimicrobials the sensitivity profile to E. coli isolated from urocultures of women treated at Basic Health Units and Emergency Care Units of Londrina- Paraná- Brazil during a period of 12 months (June 1, 2016 to June 1, 2017). METHODOLOGY: A cross-sectional study was carried out from June 2016 to June 2017. All urine samples collected in the Basic Health Units and Emergency Departments in the city of Londrina (Paraná State, Brazil) were sent to a Central Laboratory where the identification and antimicrobial susceptibility testing were performed. Clinical Laboratory Standards Institute (CLSI) breakpoints were used for the interpretation of susceptibility testing results. RESULTS: 56,555 urine cultures were performed in the period, of which 8,832 were positive, of which 5,377 were women. Of these samples, 4.7% were enterobacteria producing extended-spectrum beta-lactamases (ESBL) and 15.5% resistant to quinolones. TMP- SMX was resistant in more than 30% of the samples in all age groups. Among quinolone-resistant isolates, resistance to cephalothin, ampicillin and sulfamethoxazole-trimethoprim was greater than 60%. Nitrofurantoin was the only antimicrobial that showed 90% of sensitivity. CONCLUSION: The antimicrobials sensitivity profile was similar to that reported in the literature, with TMP- SMX resistance greater than 30% in the studied samples. Nitrofurantoin maintains high sensitivity rates greater than 90%. Resistance to quinolones increases proportionally with age, as well ESBL.

Setting up criteria for drug-induced autoimmune-like hepatitis through a systematic analysis of published reports.

Nitrofurantoin, minocycline, methyldopa and infliximab, have been found to induce autoimmune-like hepatitis (DI-AILH). Evidence for other drugs and herbal and dietary supplements (HDS) is unclear. The aims of the study were to establish criteria to define and review the published evidence of suspected DI-AILH. Search was undertaken in Pubmed using search terms "drug-induced liver injury," "autoimmune hepatitis," and "drug-induced autoimmune hepatitis." DI-AILH was defined as (1) drug as a potential trigger of liver injury with autoimmune features and histological findings compatible with AIH; (2) no or incomplete recovery or worsening of liver tests after discontinuation of the drug; (3) corticosteroids requirement or spontaneous recovery; (4) follow-up without immunosuppression (IS) and no relapse of AIH at least 6 months after discontinuation of IS; and (5) drugs potentially inducing AILH with a chronic course. Cases fulfilling the first four criteria were considered probable DI-AILH with three possible DI-AILH. A total of 186 case reports were identified for conventional drugs (n = 148; females 79%; latency 2.6 months) and HDS (n = 38; females 50%). The most commonly reported agents of DI-AILH were interferons (n = 37), statins (n = 24), methylprednisolone (MPS) (n = 16), adalimumab (n = 10), imatinib (n = 8), and diclofenac (n = 7). Tinospora cordifolia and Khat were the only HDS with probable DI-AILH cases. No relapses of AIH were observed when IS was stopped after interferons, imatinib, diclofenac, and methylprednisolone. Conclusion: Beyond well-recognized nitrofurantoin, methyldopa, hydralazine, minocycline, and infliximab as causes of DI-AILH, interferons, imatinib, adalimumab, and MPS were the best-documented agents leading to probable DI-AILH. Khat and Tinospora cordifolia were the only HDS found to be able to induce DI-AILH. Long-term immunosuppression appears to be rarely required in patients with DI-AILH due to these drugs.

Antibiogram and molecular characterization of multi-drug resistant microorganisms isolated from urinary tract infections.

Bacteria are the commonest etiological factor among the microbes that cause UTIs. The most prevalent bacteria identified in the lab are Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa. Antibiotics are the empiric therapy for such infections but the reoccurrence rate is becoming high owing to the development of resistance due to their irrational and indiscriminate use across the globe. This study was designed on UTI cases of OPD, Medical, Nephrology, Surgical, Main OT, Urology and ICU wards of Allied hospital Faisalabad. 11 antibiotics were used which showed that E. coli is sensitive to Amikacin, Gentamicin, Imipenem, Piperacillin tazobactam, and Polymyxin B. Klebsiella pneumonia showed sensitivity for Amikacin, Gentamicin, Nitrofurantoin, Imipenem, Polymyxin B, Piperacillin tazobactam and Trimethoprim-sulfamethoxazole. While Pseudomonas aurignosa showed resistance to Amikacin, Ciprofloxacin, Gentamicin, Piperacillin tazobactam, Imipenem, and Polymyxin B. E. coli exhibited the highest sensitivity for Piperacillin tazobactam, Klebsiella pneumonia for Imipenem and Pseudomonas aurignosa for Ciprofloxacin. Further, the isolated DNA samples of these microorganisms were confirmed by gel electrophoresis and subjected to molecular characterization by performing trace file and phylogenetic tree analysis.

Office-based approach to urinary tract infections in 50 000 patients: results from the REWIND study.

OBJECTIVES: The REWIND study sought to describe the real-world clinical and prescribing practices for the management of urinary tract infection (UTI) in Italy, Belgium, Russia and Brazil in order to compare current practices with international, European and national guidelines. METHODS: An integrated mixed-methods approach was adopted that used information from primary care electronic medical records in longitudinal patient databases available in Italy and Belgium, and surveys of physicians in Russia (general practitioners) and Brazil (gynaecologists). RESULTS: In total, 49 548 female patients were included in the study. Antibiotics were the most common management option for UTI in Italy (71.1%, n=27 600), Belgium (92.4%, n=7703), Russia (81.9%, n=1231) and Brazil (82.4%, n=740). Fosfomycin trometamol was the first-choice antibiotic for the treatment of UTI in all countries. Ciprofloxacin was also commonly prescribed in Italy (24.6%, n=6796), Belgium (17.8%, n=1373), Russia (14.9%, n=184) and Brazil (9.6%, n=71), while prescription of nitrofurantoin was common in Belgium (24.5%, n=1890) alone. CONCLUSIONS: Despite differences in study designs and data sources, fosfomycin trometamol was found to be the most commonly prescribed treatment for UTI in all participating countries. In Belgium, real-world prescribing practices for UTI adhered more closely to European guidelines than national guidelines. Although not recommended in international and European guidelines for lower UTI management, the use of fluoroquinolones was still widespread.

The Impact of Breast Cancer Resistance Protein (BCRP/ABCG2) on Drug Transport Across Caco-2 Cell Monolayers.

Breast cancer resistance protein (BCRP) is expressed on the apical membrane of small intestinal epithelial cells and functions as an efflux pump with broad substrate recognition. Therefore, quantitative evaluation of the contribution of BCRP to the intestinal permeability of new chemical entities is very important in drug research and development. In this study, we assessed the BCRP-mediated efflux of several model drugs in Caco-2 cells using WK-X-34 as a dual inhibitor of P-glycoprotein (P-gp) and BCRP and LY335979 as a selective inhibitor of P-gp. The permeability of daidzein was high with an apparent permeability coefficient for apical-to-basal transport (P AB) of 20.3 × 10-6 cm/s. In addition, its efflux ratio (ER) was 1.55, indicating that the contribution of BCRP to its transport is minimal. Estrone-3-sulfate and ciprofloxacin showed relatively higher ER values (>2.0), whereas their BCRP-related absorptive quotient (AQ BCRP) was 0.21 and 0.3, respectively. These results indicate that BCRP does not play a major role in regulating the permeability of estrone-3-sulfate and ciprofloxacin in Caco-2 cells. Nitrofurantoin showed a P AB of 1.8 × 10-6 cm/s, and its ER was 7.6. However, the AQ BCRP was 0.37, suggesting minimal contribution of BCRP to nitrofurantoin transport in Caco-2 cells. In contrast, topotecan, SN-38, and sulfasalazine had low P AB values (0.81, 1.13, and 0.19 × 10-6 cm/s, respectively), and each AQ BCRP was above 0.6, indicating that BCRP significantly contributes to the transport of these compounds in Caco-2 cells. In conclusion, Caco-2 cells are useful to accurately estimate the contribution of BCRP to intestinal drug absorption. SIGNIFICANCE STATEMENT: We performed an in vitro assessment of the contribution of breast cancer resistance protein (BCRP) to the transport of BCRP and/or P-glycoprotein (P-gp) substrates across Caco-2 cell monolayers using absorptive quotient, which has been proposed to represent the contribution of drug efflux transporters to the net efflux. The present study demonstrates that the combined use of a BCRP/P-gp dual inhibitor and a P-gp selective inhibitor is useful to estimate the impact of BCRP and P-gp on the permeability of tested compounds in Caco-2 cells.

Use of other antimicrobial drugs is associated with trimethoprim resistance in patients with urinary tract infections caused by E. coli.

In recent years, high frequencies of trimethoprim resistance in urinary tract infections (UTIs) caused by E. coli are have been reported. Co-resistance to other antimicrobial drugs may play a role in this increase. Therefore, we investigated whether previous use of other antimicrobial drugs was associated with trimethoprim resistance. We conducted a nested case-control study with urinary cultures with E. coli from participants of the Rotterdam Study sent in by general practitioners to the regional laboratory between 1 January 2000 and 1 April 2016. Multivariable logistic regression analysis was performed to study the association between prior prescriptions of several antimicrobial drug groups and trimethoprim resistance using individual participant data. Urinary cultures of 1264 individuals with a UTI caused by E. coli were included. When adjusted for previous other antimicrobial drug use, a history of > 3 prescriptions of extended-spectrum penicillins (OR 1.68; 95% CI 1.10-2.55) was significantly associated with trimethoprim resistance of E. coli as was the use of > 3 prescriptions of sulfonamides and trimethoprim (OR 2.22; 95% CI 1.51-3.26). The use of > 3 prescriptions of nitrofuran derivatives was associated with a lower frequency of trimethoprim resistance (OR 0.60; 95% CI 0.39-0.92), after adjustment for other antimicrobial drug prescriptions. We found that previous use of extended-spectrum penicillins is associated with trimethoprim resistance. On the contrary, previous nitrofurantoin use was associated with a lower frequency of trimethoprim resistance. Especially in individuals with recurrent UTI, co-resistance should be taken into account and susceptibility testing before starting trimethoprim should be considered.

Ibuprofen lacks direct antimicrobial properties for the treatment of urinary tract infection isolates.

The high incidence of urinary tract infection (UTI) among women and children, in combination with a lack of antibiotic efficacy with regard to pathogen eradication and recurrence prevention, as well as the negative side effects associated with antibiotics, has led researchers to explore the role of non-steroidal anti-inflammatory drugs as a primary management strategy. The aim of this study was to determine whether ibuprofen (IBU) or one of its major metabolites, 2-carboxyibuprofen (CIBU), could affect the growth and adhesion of the two most common uropathogens, Escherichia coli and Enterococcus faecalis. The bacterial growth and adhesion to the urothelial cells of E. coli UTI89 and E. faecalis 1131 in the presence of physiologically relevant concentrations of IBU and CIBU were assessed. The effect of IBU on bacterial adhesion to urothelial cells was also assessed following exposure to trimethoprim/sulfamethoxazole (TMP/SMX) and nitrofurantoin. Bacterial growth was not affected by IBU. Further, only at high levels of IBU not regularly found in the bladder was there a significant increase in E. faecalis 1131 attachment at growth inhibitory concentrations of TMP/SMX. There was no effect on the attachment of E. faecalis or E. coli to urothelial cells in the presence of nitrofurantoin. These studies indicate that the beneficial effects of IBU for UTI management are likely mediated through its anti-inflammatory properties rather than direct interactions with uropathogens in the bladder.

Uncomplicated urinary tract infections in Swedish primary care; etiology, resistance and treatment.

BACKGROUND: Uncomplicated urinary tract infection (uUTI) is common and a majority of patients are prescribed antibiotics. There is little knowledge about antibiotic resistance in urine samples from patients with uUTI in primary health care (PHC). The aim was to describe antibiotic treatment, bacterial findings, the prevalence of resistant E.coli and factors associated with antibiotic resistance. The aim was also to compare the prevalence of resistant E.coli in clinical practice with the prevalence of resistant E.coli in routine microbiological laboratory data. METHODS: This observational study in PHC setting started in November 2014 and ended in March 2016. Women aged 17 years and older with symptoms indicating uUTI from eight PHCs were included. Questionnaires were used to retrieve anamnestic data. All urine samples were sent to the local laboratory of microbiology for diagnostic analysis and susceptibility testing. Proportions of resistant E.coli were compared with corresponding data from the regional laboratory. RESULTS: Urine cultures were analysed in 304 women with a median age of 46 (IQR 32-66) years. Bacterial growth was found in 243 (80%) of urine samples, and E.coli in 72% of the positive samples. A total of 80% of detected E.coli isolates were susceptible to all tested antimicrobials and resistance rates to ciprofloxacin were lower than reported from the local clinical laboratory. Antibiotic treatment within the last year was independently associated with antibiotic resistant E.coli in the urine sample adjusted OR 4.97 (95% CI 2.04-12.06). A total of 74% of the women were treated with antibiotics. The most prescribed was pivmecillinam followed by nitrofurantoin. CONCLUSIONS: Antibiotic resistance in E.coli was low. Antibiotic treatment within the last year was associated with antibiotic resistant E.coli. Data from the clinical microbiology laboratory indicates that laboratory data may overestimate antibiotic resistance and lead to an unnecessary change in empiric antibiotic treatment of uUTI in primary care. The empirically prescribed antibiotics, were inline with Swedish treatment recommendations for uUTI.

Sensibilidad a nitrofurantoína en el uropatógeno intrahospitalario E. Coli procedente de pacientes gerontes hospitalizados / Snsitivity to nitrofurantoin of urocultures from hospitalized gerontes with E. Coli from urinary tract infections

En la presente investigación se determinó la sensibilidad a nitrofurantoína (NTF) mediante un análisis observacional retrospectivo de informes de antibiogramas, por disco de difusión, de urocultivos provenientes de gerontes hospitalizados. En la serie observada (N=90) el desarrollo más frecuente fue E. Coli que presentó una sensibilidad a NTF de 100%. Al considerar la sensibilidad total (es decir de todos las bacterias uropatógenas Gram negativas, (BGN) la resistencia para NTF fue de 26%. Se debate además sus limitaciones médicas y algunos de los potenciales usos de NTF en pacientes hospitalizados

In the present investigation, sensitivity to nitrofurantoin (NTF) was determined through a retrospective observations analysis of reports of antibiograms, by diffusion disc, of urocultures from hospitalized gerontes. In the series observed (N=90), the most frequent development was E. coli, which showed a sensitivity to NTF of 100%. When considering the total sensitivity (ie of all Gram-negative uropathogenic bacteria, BGN) the resistance for NTF was 26%. It also discusses its medical limitations and some of the potential uses of NTF in hospitalized patients

Enterococcus faecalis persistence in pediatric patients treated with antibiotic prophylaxis for recurrent urinary tract infections.

AIM: Enterococcus faecalis is one of the most common causes of recurrent urinary tract infection (RUTI), yet enterococcal pathogenesis is poorly understood. Our aims were to identify the prevalence of enterococci in RUTI patients and characterize the enterococcal response to nitrofurantoin and trimethoprim-sulfamethoxazole. MATERIALS & METHODS: We studied pediatric patients receiving antibiotic prophylaxis and those only under clinical observation for 12 months (n = 39). We then assessed the response of uropathogenic E. faecalis to nitrofurantoin and trimethoprim-sulfamethoxazole. RESULTS: Enterococci were isolated from almost half of patients and exposure of Enterococcus to nitrofurantoin increased virulence properties; this did not correlate with increased expression of virulence factors. CONCLUSION: Our results demonstrate that antibiotic prophylaxis may not be suitable for treatment of enterococcal RUTI (NCT02357758).

Epizootics of Pseudomonas anguilliseptica among cultured seabream (Sparus aurata) populations: Control and treatment strategies.

The present study was investigating the clinical pictures, prevalence, as well as the ecological conditions associated with Pseudomonas anguilliseptica outbreaks in four cultured seabream, Sparus aurata farms at different localities in Egypt during winter of 2016. The phenotypic and genotypic patterns of Pseudomonas isolates were investigated. The existence of intraspecific heterogeneity among different isolates was analyzed using Restriction Fragment Length Polymorphism (RFLP) technique. Attempts on disease control using antibiogram or dietary supplement were also considered. To achieve these goals, various commercial antibiotic discs were analyzed against Ps. anguilliseptica isolates using the disc diffusion method. Additionally, the impact of one-month dietary incorporation with 3% garlic extract or 0.5% potassium diformate on S. aurata viability and response for prolonged bathing treatment with florfenicol was evaluated following challenge with the virulent strain of Ps. anguilliseptica. Most of the naturally infected fish displayed spiral-swimming behavior with no obvious external lesions. The prevalence of infections in the four investigated farms (F1, F2, F3, and F4) were 44.9, 69.04, 67.72, and 83.4%, respectively. Water analysis revealed a significant variation in total hardness, pH, dissolved oxygen (D.O), ammonia and salinity among different localities. All isolates were rather uniform in most of the biochemical characteristics and were identical on the basis of RFLP analysis. The analyses of PAF-PAR gene pointed out specific amplification bands of 439 bp length. The antibiogram revealed a potential activity of florfenicol, ciprofloxacin, nitrofurantoin, and oxytetracycline against all isolates. Experimentally challenged fish fed on garlic extract or potassium diformate presented lower mortality and better therapeutic response to florfenicol than those fed on a normal basal diet. In conclusion, Ps. anguilliseptica is a prevalent pathogen among cultured seabream where dietary inclusion of 3% garlic extract or 0.5% potassium diformate seemed to improve seabream health status and subsequently, increase the efficacy of the treatment with the selective antibiotic.

[Treatment of vancomycin-resistant enterococcal infections].

Vancomycin-resistant enterococci (VRE) are a growing healthcare concern, and since 2012 the incidence has increased eightfold in Denmark. Treatment options for infections with ampicillin-resistant VRE are sparse, and there are no Danish guidelines concerning this topic. For treatment of uncomplicated VRE urinary tract infections, ciprofloxacin or nitrofurantoin can be used. The mainstay of treatment of bacteraemia and other severe infections caused by VRE is linezolid or high-dose daptomycin. Combination treatment is recommended for complicated infections and/or prolonged therapy.