Bacteriological profile, antimicrobial susceptibility, and factors associated with urinary tract infection in pregnant women.

INTRODUCTION: Urinary tract infection (UTI) is a common bacterial complication in pregnancy. The study aimed to estimate the prevalence, risk factors, and bacterial etiology of UTI during pregnancy and determine the efficacy of antimicrobial drugs in treating UTIs. METHODOLOGY: Urine specimens and clinical data were collected from pregnant women who attended primary health centers in Erbil, Iraq. All specimens were cultured on appropriate media and identified by standard microbiological methods. The pregnant women were grouped into symptomatic UTI group, asymptomatic bacteriuria group, and the control group. The agar dilution method was used to determine antimicrobial susceptibility. RESULTS: Among the 5,042 pregnant women included in this study, significant bacteriuria was found in 625 (12.40%) of the cases, and 198 (31.68%) had symptomatic UTI, of which 43.59% were diagnosed during the third trimester. Out of the 643 bacteria isolated, 33.28% were symptomatic UTI, of which 43.59% developed during the third trimester. There was a significant difference in the bacterial etiology between symptomatic UTI and asymptomatic bacteriuria (p = 0.002), as well as between cystitis and pyelonephritis (p = 0.017). The most common bacterial species isolated was Escherichia coli, which was susceptible to fosfomycin (100%), meropenem (99.45%), and nitrofurantoin (97.8%). CONCLUSIONS: Pregnant women are more likely to develop UTI in the third trimester. Escherichia coli is the predominant pathogen. The study suggests the use of fosfomycin, meropenem, and nitrofurantoin for the treatment of UTI. No Gram-positive isolates were resistant to daptomycin.

Susceptibility to Fosfomycin and Nitrofurantoin of ESBL-Positive Escherichia coli and Klebsiella pneumoniae Isolated From Urine of Pediatric Patients.

BACKGROUND: Pediatric urinary tract infection (UTI) caused by extended-spectrum ß-lactamase (ESBL)-positive gram-negative bacilli (GNB) has limited options for oral antibiotic treatment. The purpose of this study was to investigate the susceptibility of ESBL-positive Escherichia coli and Klebsiella pneumoniae isolates from pediatric urine samples to two oral antibiotics (fosfomycin and nitrofurantoin). METHODS: From November 2020 to April 2022, ESBL-positive E. coli and K. pneumoniae isolates from urine samples were collected at Samsung Medical Center, Seoul, Korea. Patients over 18 years of age or with malignancy were excluded. For repeated isolates from the same patient, only the first isolate was tested. Minimum inhibitory concentrations (MICs) were measured using agar (fosfomycin) or broth (nitrofurantoin) dilution methods. MIC50 and MIC90 were measured for fosfomycin and nitrofurantoin in both E. coli and K. pneumoniae. RESULTS: There were 117 isolates from 117 patients, with a median age of 7 months (range, 0.0-18.5 years). Among 117 isolates, 92.3% (108/117) were E. coli and 7.7% (9/117) were K. pneumoniae. Isolates from the pediatric intensive care unit (PICU) and general ward (GW) was 11.1% (13/117) and 88.9% (104/117), respectively. Among 108 E. coli isolates, MIC50 and MIC90 for fosfomycin were 0.5 µg/mL and 2 µg/mL, respectively. Fosfomycin susceptibility rate was 97.2% (105/108) with a breakpoint of 128 µg/mL. Fosfomycin susceptibility rate was significantly lower in PICU isolates than in GW isolates (81.8% vs. 99.0%, P = 0.027). For nitrofurantoin, both the MIC50 and MIC90 were 16 µg/mL. Nitrofurantoin susceptibility rate was 96.3% (104/108) with a breakpoint of 64 µg/mL based on Clinical and Laboratory Standards Institute guidelines. Among the nine K. pneumoniae isolates, the MIC50 and MIC90 for fosfomycin was 2 µg/mL and 32 µg/mL, respectively. MIC50 and MIC90 for nitrofurantoin were 64 µg/mL and 128 µg/mL, respectively. CONCLUSION: For uncomplicated UTI caused by ESBL-positive GNB in Korean children, treatment with fosfomycin and nitrofurantoin for E. coli infections can be considered as an effective oral therapy option.

Oral administration of an extended-release formulation of nitrofurantoin results in high concentrations in the urine of dogs.

OBJECTIVE: Sporadic bacterial cystitis in both dogs and humans is often caused by Escherichia coli. In humans, nitrofurantoin is a first-line antimicrobial for the treatment of bacterial cystitis but in dogs a lack of available data may be part of the reason it is only recommended as a second-line treatment. The objective of this preliminary study was to determine the plasma pharmacokinetics and urine concentrations of nitrofurantoin monohydrate-macrocrystalline in dogs. ANIMALS: 8 healthy female hound dogs. PROCEDURES: From July 26 to July 28, 2021, dogs received a single oral dose of nitrofurantoin monohydrate-macrocrystalline 100 mg with food. Blood and urine were collected at predetermined times. Nitrofurantoin concentrations were assayed by UPLC-MS/MS and plasma data were analyzed using noncompartmental methods. RESULTS: Plasma concentrations were low for all dogs with a mean ± SD maximum concentration (Cmax) of 0.242 ± 0.098 µg/mL (range, 0.14 to 0.42 µg/mL) occurring between 2 and 24 hours. Urine concentrations were manyfold higher than for plasma. Cmax in urine was 134 ± 54 µg/mL (range, 49.1 to 218 µg/mL) occurring between 6 and 36 hours. As seen in other species, nitrofurantoin concentrated in urine with concentrations being 500 times higher than the concentration in plasma. CLINICAL RELEVANCE: Results suggested that nitrofurantoin monohydrate-macrocrystalline formulation of nitrofurantoin should be effective in treating bacterial cystitis caused by susceptible uropathogens.

Inclusion of Nitrofurantoin into the Realm of Cancer Chemotherapy via Biology-Oriented Synthesis and Drug Repurposing.

Structural modifications of the antibacterial drug nitrofurantoin were envisioned, employing drug repurposing and biology-oriented drug synthesis, to serve as possible anticancer agents. Eleven compounds showed superior safety in non-cancerous human cells. Their antitumor efficacy was assessed on colorectal, breast, cervical, and liver cancer cells. Three compounds induced oxidative DNA damage in cancer cells with subsequent cellular apoptosis. They also upregulated the expression of Bax while downregulated that of Bcl-2 along with activating caspase 3/7. The DNA damage induced by these compounds, demonstrated by pATM nuclear shuttling, was comparable in both MCF7 and MDA-MB-231 (p53 mutant) cell lines. Mechanistic studies confirmed the dependence of these compounds on p53-mediated pathways as they suppressed the p53-MDM2 interaction. Indeed, exposure of radiosensitive prostatic cancer cells to low non-cytotoxic concentrations of compound 1 enhanced the cytotoxic response to radiation indicating a possible synergistic effect. In vivo antitumor activity was verified in an MCF7-xenograft animal model.

Exploration of ethylene glycol linked nitrofurantoin derivatives against Leishmania: Synthesis and in vitro activity.

Leishmaniasis is a neglected tropical disease that is caused by the Leishmania parasite. It is estimated that there are more than 350 million people at risk of infection annually. Current treatments that are in clinical use are expensive, have toxic side effects, and are facing parasitic resistance. Therefore, new drugs are urgently required. In the quest for new, safe, and cost-effective drugs, a series of novel ethylene glycol derivatives of nitrofurantoin was synthesised and the in vitro antileishmanial efficacy of the compounds tested against Leishmania donovani and Leishmania major strains. Arylated ethylene glycol derivatives were found to be the most potent, with submicromolar activity up to 294-fold greater than the parent compound nitrofurantoin. Analogues 2j and 2k had the best antipromastigote activities with submicromolar IC50 values against L. major IR-173 and antimonial-resistant L. donovani 9515 strains.

Dynamics of microbial communities during biotransformation of nitrofurantoin.

The purpose of this research was to investigate the biodegradation of nitrofurantoin (NFT), a typical nitrofuran antibiotic of potential carcinogenic properties, by two microbial communities derived from distinct environmental niches - mountain stream (NW) and seaport water (SS). The collected environmental samples represent the reserve of the protected area with no human intervention and the contaminated area that concentrates intense human activities. The structure, composition, and diversity of the communities were analyzed at three timepoints during NFT biodegradation. Comamonadaceae (43.2%) and Pseudomonadaceae (19.6%) were the most abundant families in the initial NW sample. The top families in the initial SS sample included Aeromonadaceae (31.4%) and Vibrionaceae (25.3%). The proportion of the most abundant families in both consortia was remarkably reduced in all samples treated with NFT. The biodiversity significantly increased in both consortia treated with NFT suggesting that NFT significantly alters community structure in the aquatic systems. In this study, NFT removal efficiency and transformation products were also studied. The biodegradation rate decreased with the increasing initial NFT concentration. Biodegradation followed similar pathways for both consortia and led to the formation of transformation products: 1-aminohydantoin, semicarbazide (SEM), and hydrazine (HYD). SEM and HYD were detected for the first time as NFT biotransformation products. This study demonstrates that the structure of the microbial community may be directly correlated with the presence of NFT. Enchanced biodiversity of the microbial community does not have to be correlated with increase in functional capacity, such as the ability to biodegradation because higher biodiversity corresponded to lower biodegradation. Our findings provide new insights into the effect of NFT contamination on aquatic microbiomes. The study also increases our understanding of the environmental impact of nitrofuran residues and their biodegradation.

[Rationale for choosing an antibiotic for the treatment of cystitis: recommendations of clinical pharmacologists: A review].

In recent years, the harmonization of domestic and foreign clinical recommendations for the treatment of cystitis has been achieved. Nitrofurans and fosfomycin trometamol are recommended as first line therapy antibiotics, and oral 3rd generation of cephalosporins are recommended as alternative antibiotics; fluoroquinolones are excluded from the recommended medications due to an unfavorable safety profile. The main rationale for inclusion of antibiotics in the recommendations as a first line therapy of cystitis is the level of resistance of uropathogens to antibiotics, primarily Escherichia coli. Stable low level of resistance of E. coli in Russia was noted to nitrofurans and fosfomycin (5%), higher to cephalosporins. Among nitrofurans, furazidine is characterized by higher activity against E. coli compared to nitrofurantoin. The potassium salt of furazidine in dosage form with magnesium carbonate is preferred, since it is characterized by higher bioavailability and provides a therapeutic level of concentrations in urine above the MIC during the entire dosing period. Due to the global increase in the resistance of uropathogens observed in recent years, experts have begun to pay more and more attention to the ecological safety of antimicrobial therapy in order to minimize the risk of concomitant (collateral) damage, contributing to the selection of multi-drug resistant strains of microorganisms. In the latest WHO document of 2021, experts divided antibiotics into three groups (ACCESS, WATCH, RESERVE) according to the priority of choice. The ACCESS group of drugs for the treatment of cystitis includes nitrofurantoin and furazidine as agents with minimal collateral effect, while fosfomycin trometamol and cephalosporins are listed in the WATCH group. Thus, from the standpoint of ecological safety, WHO experts recommend prescribing nitrofurans in the treatment of cystitis in the first line of therapy.

SUsceptibility and Resistance to Fosfomycin and other antimicrobial agents among pathogens causing lower urinary tract infections: findings of the SURF study.

Urinary tract infections (UTIs) are prevalent worldwide, particularly among women. Their incidence increases with age, and treatment is increasingly challenging owing to antibiotic resistance and the lack of new agents. We investigated the susceptibility of current urinary isolates to fosfomycin and other antibiotics across Europe. This cross-sectional study collected consecutive urinary isolates from non-hospitalised women at 20 centres in Belgium, the UK, Italy, Spain and Russia. Bacteria were tested by disk diffusion with relevant antibiotics. As a quality control, a central laboratory re-tested, by agar dilution, (i) isolates found resistant to fosfomycin and (ii) every tenth isolate; all non-Russian sites were included. A total of 2848 isolates were analysed, principally Escherichia coli (2064; 72.5%), Klebsiella spp. (275; 9.7%) and Proteus spp. (103; 3.6%). For E. coli, agents active against >90% of isolates were nitrofurantoin (98.5%), fosfomycin (96.4%) and mecillinam (91.8%). Fosfomycin and nitrofurantoin remained active against >90% of cephalosporin-resistant E. coli. Among 143 E. coli recorded as susceptible locally by disk tests, 138 (96.5%) were confirmed susceptible by minimum inhibitory concentration (MIC) tests, however resistance was only confirmed in 29/58 (50.0%) of those reported resistant by local disk tests. Escherichia coli was found to be the most common uropathogen isolated and was highly susceptible to fosfomycin, nitrofurantoin and mecillinam, all used effectively for more than 30 years. Guidelines advocating fosfomycin for uncomplicated UTIs in women remain microbiologically valid.

Alkaline Urine in the Emergency Department Predicts Nitrofurantoin Resistance.

BACKGROUND: The Proteeae group (i.e., Proteus species, Morganella morganii, and Providencia species) frequently causes urinary tract infections (UTIs) and is generally resistant to nitrofurantoin. Proteeae species can produce urease, which can increase urine pH. OBJECTIVE: Our aim was to determine whether higher urine pH in the emergency department is associated with nitrofurantoin resistance. METHODS: A single health system database of emergency department patients aged 18 years and older who received urinalysis between April 18, 2014, and March 7, 2017, was examined using χ2 test and multivariable regression analysis. RESULTS: Of 67,271 urine samples analyzed, 13,456 samples grew a single bacterial species. Urine cultures growing the Proteeae group were associated with significantly more alkaline urine than other bacteriuria cultures (odds ratio [OR] 2.20, 95% confidence interval [CI] 2.06-2.36; p < 0.001). The Proteeae species represented 4.4% of urine samples at pH 5-7, 24.4% at pH 8-9, and 40.0% at pH 9. At urine pH 5-7, 80.4% of urine samples were sensitive to nitrofurantoin; however, this percentage decreased to 66.1% for urine pH 8-9 and 54.6% for urine pH 9. Nitrofurantoin had the highest OR (2.10, 95% CI 1.85-2.39) among cefazolin, ciprofloxacin, and trimethoprim/sulfamethoxazole for bacteriuria sensitive to those antibiotics at urine pH 5-7. At urine pH 8-9 and 9, nitrofurantoin had the lowest OR among the antibiotics: 0.48 (95% CI 0.42-0.54) and 0.31 (95% CI 0.24-0.40), respectively (p < 0.001 for both). CONCLUSIONS: Urine pH of 8 or higher is associated with high rates of nitrofurantoin resistance.

Stimulation of de novo glutathione synthesis by nitrofurantoin for enhanced resilience of hepatocytes.

Toxicity is not only a function of damage mechanisms, but is also determined by cellular resilience factors. Glutathione has been reported as essential element to counteract negative influences. The present work hence pursued the question how intracellular glutathione can be elevated transiently to render cells more resistant toward harmful conditions. The antibiotic nitrofurantoin (NFT) was identified to stimulate de novo synthesis of glutathione in the human hepatoma cell line, HepG2, and in primary human hepatocytes. In intact cells, activation of NFT yielded a radical anion, which subsequently initiated nuclear-factor-erythroid 2-related-factor-2 (Nrf2)-dependent induction of glutamate cysteine ligase (GCL). Application of siRNA-based intervention approaches confirmed the involvement of the Nrf2-GCL axis in the observed elevation of intracellular glutathione levels. Quantitative activation of Nrf2 by NFT, and the subsequent rise in glutathione, were similar as observed with the potent experimental Nrf2 activator diethyl maleate. The elevation of glutathione levels, observed even 48 h after withdrawal of NFT, rendered cells resistant to different stressors such as the mitochondrial inhibitor rotenone, the redox cycler paraquat, the proteasome inhibitors MG-132 or bortezomib, or high concentrations of NFT. Repurpose of the antibiotic NFT as activator of Nrf2 could thus be a promising strategy for a transient and targeted activation of the endogenous antioxidant machinery. Graphical abstract.

Resistencia a nitrofuranos en Salmonella enterica aisladas de carne para consumo humano / Nitrofuran resistance in Salmonella enterica isolated from meat for human consumption

RESUMEN En el presente estudio, se analizaron los mecanismos de resistencia a nitrofuranos en 18 muestras cár nicas con Salmonella enterica (15 de pollo, 2 de ternera y 1 de cerdo) de mercados de Lima (Perú). Determinaron los serotipos de los aislamientos y la sensibilidad a furazolidona y nitrofurantoina (con y sin el inhibidor de bombas de expulsión Phenyl-Arginine-β-Naphthylamide [PAβN]), las mutaciones en los genes snrA y cnr por PCR y la transferabilidad de la resistencia por conjugación. Se identificaron 15 muestras con S. infantis (13 muestras de pollo), 2 con S. enteritidis y 1 con S. anatum. Todos los aisla mientos, excepto S. anatum, fueron resistentes a ambos nitrofuranos (concentración mínima inhibidora [CMI] a furazolidona: 32-64 µg/mL, CMI a nitrofurantoina: 128-256 µg/mL), sin diferencias al adicio narse PAβN. Todos los aislamientos resistentes a nitrofuranos presentaron sustituciones en snrA y cnr (S. infantis: snrA STOP-151; cnr STOP-137; S. enteritidis: snrA STOP-180; cnr STOP-179). No se detectaron mecanismos transferibles de resistencia a nitrofuranos.

ABSTRACT The mechanisms of resistance to nitrofurans from 18 meat samples with Salmonella enterica (chicken: 15; beef: 2; pork: 1) collected in Lima (Peru) were analyzed. The isolates were serotyped and the susceptibility levels to furazolidone and nitrofurantoin [with and without the efflux pump inhibitor Phenyl-Arginine- β-naphthylamide (PAβN)], the presence of mutations in the snrA and cnr genes and the transferability of resistance by conjugation were established. Fifteen samples with S. infantis (13 from chicken samples), 2 with S. enteritidis and 1 with S. anatum were identified. All isolates except the S. anatum were resistant to both nitrofurans showing MICs (minimum inhibitory concentration) of furazolidone and nitrofurantoin of 32-64 μg/mL and 128-256 μg/mL, respectively. The addition of PAßN had no effect on the MIC levels. All nitrofuran-resistant isolates showed amino acid codon alterations at both snrA and cnr (S. infantis: snrA STOP-151; cnr STOP-137; S. enteritidis: snrA STOP-180; cnr STOP-179). No transferable mecha nisms of nitrofuran resistance were detected.

Optimizing dosing of nitrofurantoin from a PK/PD point of view: What do we need to know?

Nitrofurantoin is an old antibiotic and an important first-line oral antibiotic for the treatment of uncomplicated urinary tract infections. However despite its long term use for over 60 years, little information is available with respect to its dose justification and this may be the reason of highly variable recommended doses and dosing schedules. Furthermore, nitrofurantoin is not a uniform product -crystal sizes of nitrofurantoin, and therefore pharmacokinetic properties, differ significantly by product. Moreover, pharmacokinetic profiling of some products is even lacking, or difficult to interpret because of its unstable chemical properties. Pharmacokinetic and pharmacodynamic data is now slowly becoming available. This review provides an overview of nitrofurantoins antibacterial, pharmacokinetic and pharmacodynamic properties. This shows that a clear rationale of current dosing regimens is scanty.

Antimicrobial resistance patterns in urinary E. coli isolates after a change in a single center's guidelines for uncomplicated cystitis in ambulatory settings.

Recommending nitrofurantoin to treat uncomplicated cystitis was associated with increased nitrofurantoin use from 3.53 to 4.01 prescriptions per 1,000 outpatient visits, but nitrofurantoin resistance in E. coli isolates remained stable at 2%. Concomitant levofloxacin resistance was a significant risk for nitrofurantoin resistance in E. coli isolates (odds ratio [OR], 2.72; 95% confidence interval [CI], 1.04-7.17).

Local epidemiology and resistance profiles in acute uncomplicated cystitis (AUC) in women: a prospective cohort study in an urban urological ambulatory setting.

BACKGROUND: Acute uncomplicated cystitis (AUC) is a common ailment in the urological setting. Guidelines for urinary tract infections are based on large-scale multi-centre, epidemiological and international studies. The objective of this observational study was to establish whether the results of a multi-centre study on the resistance profile of Escherichia coli (E. coli) in patients with AUC could be directly applied to an urological practice in a major European city or whether there are divergences in the resistance profile. METHODS: An observational study was applied prospectively to 502 patients with AUC between January 2015 and January 2017). Personal data were anonymised. Exclusion criteria were the patient's age (<18) and treatment with an antibiotic in the week preceding examination. RESULTS: The average age was 32 (range 18-56). The most commonly detected bacteria was E. coli with 86%, followed by Enterococcus faecalis with 10% and Klebsiella pneumoniae with 4%. Resistance tests showed E. coli to be highly sensitive to fosfomycin (99.2%), nitrofurantoin (98.1%) and cefpodoxime (92.9%). E. coli exhibited resistance to ciprofloxacin (CIP) in 15.1%, to trimethoprim/sulfamethoxazole (TRS) in 25.2% and to amoxicillin/clavulanic acid (AMC) in 34% of cases. CONCLUSION: The comparison between data from this study and data from a multi-centre European (ECO-SENSI, ECO-SENSII and the 2014 update) showed relatively good sensitivity rates for fosfomycin and nitrofurantoin but significant differences in respect of resistance levels to TRS, CIP and AMC. AUC should therefore only be treated with TRS, CIP and AMC after a susceptibility test has been carried out.

Light induced cytotoxicity of nitrofurantoin toward murine melanoma.

The cytotoxicity of nitrofurantoin (NFT) in the dark and after light exposure (UVA irradiation, λ = 385 nm) was evaluated in murine melanoma B16F10 cells. NFT induces both cell proliferation and inhibition of cell viability. The dominance of one or the other effect depends on the drug concentration, incubation time (tinc) and irradiation dose. The uptake of NFT in these cells, as well as its photocytotoxicity, reaches saturation after 24 hours of incubation. The mechanism of cell death in the dark is associated with the enzymatic release of nitric oxide (NO). The increase of NFT cytotoxicity under light irradiation is associated with the increase of NO concentration due to photorelease. NO photorelease by NFT in solution was confirmed by chemiluminescence, while NO formation in cells was confirmed by fluorescence microscopy using DAF-2DA, a specific indicator of NO in living cells. The NFT does not enter nuclei, distributing preferentially in the cell cytoplasm, as shown by fluorescence microscopy.

Sensitivity to Antibiotics of Bacteria Exposed to Gamma Radiation Emitted from Hot Soils of the High Background Radiation Areas of Ramsar, Northern Iran.

BACKGROUND: Over the past several years our laboratories have investigated different aspects of the challenging issue of the alterations in bacterial susceptibility to antibiotics induced by physical stresses. OBJECTIVE: To explore the bacterial susceptibility to antibiotics in samples of Salmonella enterica subsp. enterica serovar Typhimurium (S. typhimurium), Staphylococcus aureus, and Klebsiella pneumoniae after exposure to gamma radiation emitted from the soil samples taken from the high background radiation areas of Ramsar, northern Iran. METHODS: Standard Kirby-Bauer test, which evaluates the size of the zone of inhibition as an indicator of the susceptibility of different bacteria to antibiotics, was used in this study. RESULTS: The maximum alteration of the diameter of inhibition zone was found for K. pneumoniae when tested for ciprofloxacin. In this case, the mean diameter of no growth zone in non-irradiated control samples of K. pneumoniae was 20.3 (SD 0.6) mm; it was 14.7 (SD 0.6) mm in irradiated samples. On the other hand, the minimum changes in the diameter of inhibition zone were found for S. typhimurium and S. aureus when these bacteria were tested for nitrofurantoin and cephalexin, respectively. CONCLUSION: Gamma rays were capable of making significant alterations in bacterial susceptibility to antibiotics. It can be hypothesized that high levels of natural background radiation can induce adaptive phenomena that help microorganisms better cope with lethal effects of antibiotics.

Preferential Use of Nitrofurantoin Over Fluoroquinolones for Acute Uncomplicated Cystitis and Outpatient Escherichia coli Resistance in an Integrated Healthcare System.

OBJECTIVES To evaluate changes in outpatient fluoroquinolone (FQ) and nitrofurantoin (NFT) use and resistance among E. coli isolates after a change in institutional guidance to use NFT over FQs for acute uncomplicated cystitis. DESIGN Retrospective preintervention-postintervention study. SETTING Urban, integrated healthcare system. PATIENTS Adult outpatients treated for acute cystitis. METHODS We compared 2 time periods: January 2003-June 2007 when FQs were recommended as first-line therapy, and July 2007-December 2012, when NFT was recommended. The main outcomes were changes in FQ and NFT use and FQ- and NFT-resistant E. coli by time-series analysis. RESULTS Overall, 5,714 adults treated for acute cystitis and 11,367 outpatient E. coli isolates were included in the analysis. After the change in prescribing guidance, there was an immediate 26% (95% CI, 20%-32%) decrease in FQ use (P<.001), and a nonsignificant 6% (95% CI, -2% to 15%) increase in NFT use (P=.12); these changes were sustained over the postintervention period. Oral cephalosporin use also increased during the postintervention period. There was a significant decrease in FQ-resistant E. coli of -0.4% per quarter (95% CI, -0.6% to -0.1%; P=.004) between the pre- and postintervention periods; however, a change in the trend of NFT-resistant E. coli was not observed. CONCLUSIONS In an integrated healthcare system, a change in institutional guidance for acute uncomplicated cystitis was associated with a reduction in FQ use, which may have contributed to a stabilization in FQ-resistant E. coli. Increased nitrofurantoin use was not associated with a change in NFT resistance. Infect Control Hosp Epidemiol 2017;38:461-468.

Urinary pathogenic bacterial profile, antibiogram of isolates and associated risk factors among pregnant women in Ambo town, Central Ethiopia: a cross-sectional study.

Background: Urinary tract infection (UTI) is a well-known bacterial infection posing serious health problem in pregnant women. A study was conducted in pregnant women with the objectives of estimating prevalence of UTI, determining antibiogram of the bacterial isolates and assessment of the potential risk factors associated with UTI. Methods: A cross-sectional study design was used to collect 300 mid-stream urine samples from pregnant women from March 2016 to December, 2016. Samples were inoculated into Cysteine Lactose Electrolyte Deficient medium (CLED). Colonies from CLED were subcultured onto MacConkey and Blood agar plates. A standard agar disc diffusion method was used to determine antimicrobial susceptibility. Chi-square (X2) test & logistic regression were used to show associations between UTI and explanatory variables & identify the predictors of UTI, respectively. Results: The age of pregnant women enrolled in this study ranges from 16 to 46 years (mean ± standard deviation = 25 ± 4.7 years).The overall prevalence of UTI in pregnant women was 18.7% (95% confidence interval [CI]: 14.4-23.54%).The prevalence of symptomatic and asymptomatic UTI was 20.4% (95% CI: 13.09-29.46%) and 17.8% (95% CI: 12.70-23.83%) respectively. The predominant bacteria identified were E. coli (46.4%), S. aureus (14.3%), coagulase negative Staphylococci [CoNS] (14.3%) and Proteus species (10.6%). Majority of Gram-negative bacteria isolates were resistant to ampicillin (70%), ceftriaxon (66%), gentamicin (68%) and nitrofurantoin (64%) while 75-100% of the Gram positive isolates were resistance to ampicillin. Multiple drug resistance was observed in all of the isolates. Multivariable logistic regression revealed that the odds of acquiring UTI was 4.78 times higher in pregnant women earning monthly income of ≤500 Ethiopian Birr (21.18 USD) as compared to those earning monthly income >2001 Ethiopian Birr [84.79 USD] (P = 0.046). Similarly, the risk of UTI was higher in those who eat raw meat (OR = 2.04, 95% CI: 1.09, 3.83, P = 0.026) and had previous UTI history (OR = 2.29, 95% CI = 1.15-4.56, P = 0.019) as compared to those who eat cooked meat and had no previous history of UTI. Conclusions: The prevalence & antimicrobial resistance of uropathogens was high. Health education, continuous surveillance of UTI and their antimicrobial resistance pattern are essential to reduce the consequence of symptomatic and asymptomatic bacteriuria and multi-drug resistant bacteria in pregnant women.

An update on the management of urinary tract infections in the era of antimicrobial resistance.

Urinary tract infections (UTIs) caused by antibiotic-resistant Gram-negative bacteria are a growing concern due to limited therapeutic options. Gram-negative bacteria, specifically Enterobacteriaceae, are common causes of both community-acquired and hospital acquired UTIs. These organisms can acquire genes that encode for multiple antibiotic resistance mechanisms, including extended-spectrum-lactamases (ESBLs), AmpC- ß -lactamase, and carbapenemases. The assessment of suspected UTI includes identification of characteristic symptoms or signs, urinalysis, dipstick or microscopic tests, and urine culture if indicated. UTIs are categorized according to location (upper versus lower urinary tract) and severity (uncomplicated versus complicated). Increasing rates of antibiotic resistance necessitate judicious use of antibiotics through the application of antimicrobial stewardship principles. Knowledge of the common causative pathogens of UTIs including local susceptibility patterns are essential in determining appropriate empiric therapy. The recommended first-line empiric therapies for acute uncomplicated bacterial cystitis in otherwise healthy adult nonpregnant females is a 5-day course of nitrofurantion or a 3-g single dose of fosfomycin tromethamine. Second-line options include fluoroquinolones and ß-lactams, such as amoxicillin-clavulanate. Current treatment options for UTIs due to AmpC- ß -lactamase-producing organisms include fosfomycin, nitrofurantion, fluoroquinolones, cefepime, piperacillin-tazobactam and carbapenems. In addition, treatment options for UTIs due to ESBLs-producing Enterobacteriaceae include nitrofurantion, fosfomycin, fluoroquinolones, cefoxitin, piperacillin-tazobactam, carbapenems, ceftazidime-avibactam, ceftolozane-tazobactam, and aminoglycosides. Based on identification and susceptibility results, alternatives to carbapenems may be used to treat mild-moderate UTIs caused by ESBL-producing Enterobacteriaceae. Ceftazidime-avibactam, colistin, polymixin B, fosfomycin, aztreonam, aminoglycosides, and tigecycline are treatment options for UTIs caused by carbapenem-resistant Enterobacteriaceae (CRE). Treatment options for UTIs caused by multidrug resistant (MDR)-Pseudomonas spp. include fluoroquinolones, ceftazidime, cefepime, piperacillin-tazobactam, carbapenems, aminoglycosides, colistin, ceftazidime-avibactam, and ceftolozane-tazobactam. The use of fluoroquinolones for empiric treatment of UTIs should be restricted due to increased rates of resistance. Aminoglycosides, colistin, and tigecycline are considered alternatives in the setting of MDR Gram-negative infections in patients with limited therapeutic options.

N-pentyl-nitrofurantoin induces apoptosis in HL-60 leukemia cell line by upregulating BAX and downregulating BCL-xL gene expression.

BACKGROUND: Nitrofurantoin is a nitroderivative antibiotic that has bactericidal activity against pathogens causing urinary tract infection. A few studies have reported that nitrofurantoin has cytotoxic activity against cancer cells; however, nitrofurans remain a poorly explored class of compounds with respect to their anticancer potential. The aim of this study was to investigate the anticancer effects of a nitrofurantoin derivative, n-pentyl-nitrofurantoin (NFP), on HL-60 leukemia cells. METHODS: Cytotoxicity was assayed by the MTT assay. Cell morphology and phosphatidylserine externalization were visualized after Giemsa-May-Grunwald and annexin V staining, respectively. DNA content and mitochondrial depolarization were measured by flow cytometry. BAX and BCL-xL expression was examined by RT-PCR. RESULTS: NFP was 3.8-fold more cytotoxic against HL-60 leukemia cells than against normal cells. NFP reduced the number of viable cells 24h after the treatment with a concomitant increase in the number of apoptotic cells indicated by the externalization of phosphatidylserine, DNA fragmentation, and mitochondrial depolarization. The mRNA levels of BAX increased, whereas the mRNA levels of BCL-xL decreased. CONCLUSION: The results indicate that NFP induces apoptosis in HL-60 cells by upregulating BAX and downregulating BCL-xL.