Nitrofurantoin

Context: Trimethoprim-sulfamethoxazole (TMP-SMX) and nitrofurantoin were until recently the two drugs recommended in clinical guidelines in Israel for empiric treatment of uncomplicated urinary tract infection (UTI) in women. Objectives: The objective of this study is to evaluate the economic impact of physician nonadherence to these recommendations. Design setting and patients: Data were derived from the electronic patient records of the Leumit Health Fund. Cases of women aged 18 to 75 with a diagnosis of acute cystitis or UTI that were empirically treated with antibiotics from January 2001 to June 2002 were identified. The final sample comprised 7738 physician-patient encounters. The proportion of cases treated with each individual drug was calculated, and the excess expenditure because of non-adherence to guidelines from the perspective of the Health Maintenance Organization (HMO) was evaluated using 5 days of therapy with nitrofurantoin as the reference treatment. Results: TMP-SMX was the most frequently prescribed drug (25AE81%), followed by nitrofurantoin (14AE71%) representing a 40AE52% rate of adherence to the guidelines. Drugs from the fluoroquinolone family were prescribed in 22AE82% of cases. Cost of treatment in approximately 70% of the cases exceeded the expected cost of the guideline therapy. Conclusions: Suboptimal adherence to the guidelines resulted in a significant and avoidable waste of the health plan's resources in both drugs and money.

To estimate whether first-trimester exposure to nitrofurantoin is associated with increased malformation rates and, secondarily, to estimate whether exposure to nitrofurantoin is associated with increased rates of negative pregnancy outcomes and perinatal complications. We conducted a population-based cohort study using the Norwegian Prescription Database linked to data on all live births, stillbirths, and induced abortions after 12 weeks of gestation from The Medical Birth Registry of Norway. The study population consisted of 180,120 pregnancies in 2004-2008. The pregnancy outcomes of women who were dispensed nitrofurantoin during pregnancy were compared with the outcomes of women who were dispensed pivmecillinam (disease comparison group) and unexposed women. In all, 5,794 (3.2%) filled prescriptions for nitrofurantoin during pregnancy, 1,334 women (0.7%) in the first trimester and 979 women (0.5%) in the last 4 weeks of pregnancy. Dispensing nitrofurantoin during the first trimes...

Nitrofurantoin has been used for decades for the treatment of urinary tract infections (UTIs), but clinically significant resistance in Escherichia coli is uncommon. Nitrofurantoin concentrations in the gastrointestinal tract tend to be low, which might facilitate selection of nitrofurantoin-resistant (NIT-R) strains in the gut flora. We subjected two nitrofurantoin-susceptible intestinal E. coli strains (ST540-p and ST2747-p) to increasing nitrofurantoin concentrations under aerobic and anaerobic conditions. Whole-genome sequencing was performed for both susceptible isolates and selected mutants that exhibited the highest nitrofurantoin resistance levels aerobically (ST540-a and ST2747-a) and anaerobically (ST540-an and ST2747-an). ST540-a/ST540-an and ST2747-a (aerobic MICs of >64 g/ml) harbored mutations in the known nitrofurantoin resistance determinants nfsA and/or nfsB, which encode oxygen-insensitive nitroreductases. ST2747-an showed reduced nitrofurantoin susceptibility (aerobic MIC of 32 g/ml) and exhibited remarkable growth deficits but did not harbor nfsA/nfsB mutations. We identified a 12-nucleotide deletion in ribE, encoding lumazine synthase, an essential enzyme involved in the biosynthesis of flavin mononucleotide (FMN), which is an important cofactor for NfsA and NfsB. Complementing ST2747-an with a functional wild-type lumazine synthase restored nitrofurantoin susceptibility. Six NIT-R E. coli isolates (NRCI-1 to NRCI-6) from stools of UTI patients treated with nitrofurantoin, cefuroxime, or a fluoroquinolone harbored mutations in nfsA and/or nfsB but not ribE. Sequencing of the ribE gene in six intestinal and three urinary E. coli strains showing reduced nitrofurantoin susceptibility (MICs of 16 to 48 g/ml) also did not identify any relevant mutations. NRCI-1, NRCI-2, and NRCI-5 exhibited up to 4-fold higher anaerobic MICs, compared to the mutants generated in vitro, presumably because of additional mutations in oxygen-sensitive nitroreductases.

Objective of the study was to find out the Resistogram of the urinary isolates against different commonly prescribed antimicrobials according to CLSI guidelines. Out of total 319 test samples, in 56 cases bacterial pathogens were isolated. Among those 56 isolates only 13 were resistant to Nitrofurantoin (23.21%) where as resistance to Ciprofloxacin was found in 40 isolates(71.42%), resistance against Co-Trimoxazole was found in 27 isolates (48.21%) and surprisingly, resistance against Carbapenem antibiotics (Meropenem) was in 20 isolates (35.71%). Majority of the Nitrofurantoin resistant bacterial isolates were Klebsiella pneumoniae (4 out of 13 i.e, 30.76%). All Nitrofurantoin resistant isolates were sensitive to both Tigecycline and Colistin and the isolated Escherichia coli (two in number) were sensitive to Meropenem also. There were no other therapeutic options like Fluroquinolones or Co-trimoxazole to manage the Nitrofurantoin resistant isolates as all of them were resistant to...

A thorough understanding of solid state properties is of growing importance. It is often necessary to apply multiple techniques offering complementary information to fully understand the solid state behavior of a given compound and the relations between various polymorphic forms. The vast amount of information generated can be overwhelming and the need for more effective data analysis tools is well recognized. The aim of this study was to investigate the use of multivariate data analysis, in particular principal component analysis (PCA), for fast analysis of solid state information. The data sets analyzed covered dehydration phenomena of a set of hydrates followed by variable temperature X-ray powder diffractometry and Raman spectroscopy and the crystallization of amorphous lactose monitored by Raman spectroscopy. Identification of different transitional states upon the dehydration enabled the molecular level interpretation of the structural changes related to the loss of water, as well as interpretation of the phenomena related to the crystallization. The critical temperatures or critical time points were identified easily using the principal component analysis. The variables (diffraction angles or wavenumbers) that changed could be identified by the careful interpretation of the loadings plots. The PCA approach provides an effective tool for fast screening of solid state information. ß

Drug-induced autoimmune hepatitis (DIAIH) has been reported to be caused by several drugs. There is a lack of data comparing these patients with other patients with autoimmune hepatitis (AIH). A search was performed using the Mayo Clinic diagnostic medical index for AIH patients and DIAIH patients identified over 10 years. Individuals with overlap syndromes and decompensated liver disease were excluded. Overall, 261 patients (204 females, median age 52) were identified, and 24 (9.2%) were DIAIH cases with a median age of 53 (interquartile range, 24-61). Two drugs, nitrofurantoin (n 5 11) and minocycline (n 5 11), were the main causes. A similar proportion of DIAIH patients had positive antinuclear antibodies (83% versus 70%) and smooth muscle antibodies (50% versus 45%) as compared with AIH patients. Histological grade and stage were similar in patients with DIAIH versus AIH; however, none of the DIAIH patients had cirrhosis at baseline; this was present in 20% of matched AIH cases. Liver imaging was normal in all minocycline cases. Eight of 11 (73%) nitrofurantoin patients had abnormalities on hepatic imaging (mainly liver atrophy), a finding seen in only 8 of 33 (24%) of a random sample of the rest of the AIH group (P 5 0.0089). Corticosteroid responsiveness was similar in DIAIH and the AIH patients. Discontinuation of immunosuppression was tried and successful in 14 DIAIH cases, with no relapses (0%), whereas 65% of the AIH patients had a relapse after discontinuation of immunosuppression (P < 0.0001). Conclusion: A significant proportion of patients with AIH have drug-induced AIH, mainly because of nitrofurantoin and minocycline. These two groups have similar clinical and histological patterns. However, DIAIH patients do not seem to require long-term immunosuppressive therapy.

Purpose To test whether D-mannose powder is effective for recurrent urinary tract infection (UTI) prevention. Materials and methods After initial antibiotic treatment of acute cystitis, 308 women with history of recurrent UTI and no other significant comorbidities were randomly allocated to three groups. The first group (n = 103) received prophylaxis with 2 g of D-mannose powder in 200 ml of water daily for 6 months, the second (n = 103) received 50 mg Nitrofurantoin daily, and the third (n = 102) did not receive prophylaxis. Results Overall 98 patients (31.8 %) had recurrent UTI: 15 (14.6) in the D-mannose group, 21 (20.4) in Nitrofurantoin group, and 62 (60.8) in no prophylaxis group, with the rate significantly higher in no prophylaxis group compared to active groups (P \ 0.001). Patients in D-mannose group and Nitrofurantoin group had a significantly lower risk of recurrent UTI episode during prophylactic therapy compared to patients in no prophylaxis group (RR 0.239 and 0.335, P \ 0.0001). In active groups, 17.9 % of patients reported side effects but they were mild and did not require stopping the prophylaxis. Patients in D-mannose group had a significantly lower risk of side effects compared to patients in Nitrofurantoin group (RR 0.276, P \ 0.0001), but the clinical importance of this finding is low because Nitrofurantoin was well tolerated. Conclusions In our study, D-mannose powder had significantly reduced the risk of recurrent UTI which was no different than in Nitrofurantoin group. More studies will be needed to validate the results of this study, but initial findings show that D-mannose may be useful for UTI prevention.

Metronidazole resistance has increased world-wide, ranging from less than 10% to greater than 80% among different geographical regions. 1 Increasing antimicrobial resistance has resulted in a search for alternative antimicrobial agents, such as nitrofurantoin or furazolidone, especially for use in areas with a high prevalence of metronidazole resistance. By 1987, Helicobacter pylori had been shown to be susceptible to nitrofurantoin and nitrofurantoin was one of the ®rst drugs tried for H. pylori eradication. 2 Clinical studies showed that both nitrofurantoin monotherapy and the combination of nitrofurantoin and bismuth were ineffective for the treatment of H. pylori infections. 3, 4, 5 In retrospect, these ®nding were not unexpected because it is now recognized that monotherapies and dual therapies with an antibiotic and bismuth are not clinically useful for H. pylori infection. Nitrofurantoin and furazolidone are nitrofurans. Metronidazole is a nitroimidazole. Both the nitroimidazole and the nitrofurans are grouped as nitroheterocyclic drugs which appear to have generally similar mechanisms of action. 7±9 Furazolidone monotherapy SUMMARY Background: Antibiotic resistance has increasingly been recognized as the major cause of treatment failure for Helicobacter pylori infection. New therapies for patients with metronidazole-or clarithromycin-resistant H. pylori are needed. Aim: To investigate the role of nitrofurantoin quadruple therapy for the treatment of H. pylori. Methods: Patients with con®rmed H. pylori infection received nitrofurantoin (100 mg t.d.s.), omeprazole (20 mg b.d.), Pepto-Bismol (two tablets t.d.s.), and tetracycline (500 mg t.d.s.) for 14 days. Four or more weeks after the end of therapy, outcome was assessed by repeat endoscopy with histology and culture or urea breath testing.

Context: Current Israeli guidelines for the empiric treatment of uncomplicated urinary tract infection (UTI) in women recommend nitrofurantoin for 5 days. Some physicians nevertheless opt for ofloxacin, which should be prescribed for 3 days according to universally accepted guidelines. Objective: To evaluate the economic consequences of longer than recommended durations of antibiotic therapy in the empiric treatment of uncomplicated UTI in women. Design, Setting and Patients: Data were derived from the electronic records of one of the four health maintenance organizations in Israel. The sample included all women aged 18-75 years who were diagnosed with acute cystitis or UTI from January 2001 to June 2002 and were empirically treated with antibiotics. Of the 7738 patients identified, 1138 received nitrofurantoin and 1054 ofloxacin. The excess expenditure accrued due to longer than recommended therapy with these drugs was evaluated. Results: The rate of adherence was 22AE23% for nitrofurantoin (95% CI = 19AE81%, 24AE65%), and 4AE08% for ofloxacin (95% CI = 2AE88%, 5AE28%). The average excess expenditure per case was 5AE78 USD (US Dollar) with ofloxacin and 3AE43 USD with nitrofurantoin, resulting in an annual loss to the health maintenance organizations of 19 000 USD. When extrapolated to the national population of 6AE5 million, the loss due to inappropriate treatment of adult women is 190 000 USD.

Objective of the study was to find out the Resistogram of the urinary
isolates  against  different  commonly  prescribed  antimicrobials
according  to  CLSI  guidelines.  Out  of  total  319  test samples,  in  56
cases  bacterial  pathogens  were  isolated.  Among  those  56  isolates
only 13 were resistant to Nitrofurantoin (23.21%) where as resistance
to Ciprofloxacin was found in 40 isolates(71.42%), resistance against
Co-Trimoxazole was found in 27 isolates (48.21%) and surprisingly,
resistance  against  Carbapenem  antibiotics  (Meropenem)  was  in  20
isolates  (35.71%).  Majority  of  the  Nitrofurantoin  resistant  bacterial
isolates  were  Klebsiella  pneumoniae (4  out  of  13  i.e,  30.76%).  All
Nitrofurantoin  resistant  isolates  were  sensitive  to  both  Tigecycline
and Colistin and the isolated  Escherichia coli(two in number) were
sensitive to Meropenem also. There were no other therapeutic options
like Fluroquinolones or Co-trimoxazole to manage the Nitrofurantoin
resistant isolates as all of them were resistant tothem. Thus medical
community  should  think  twice  before  replacing  Nitrofurantoin  with
Fluroquinolones or Co-Trimoxazoles as emperical therapy.

In this work, four novel pharmaceutical cocrystals of nitrofurantoin, an antibacterial drug, with isonicotinamide, picolinamide, 2-hydroxybenzamide, and 2-aminobenzamide have been obtained and thoroughly characterized by various analytical techniques. The crystal structures of the solid forms have been elucidated by single-crystal X-ray diffraction, and the energy distribution of intermolecular interactions has been further quantified on the basis of QTAIMC analysis. Eight distinct supramolecular heterosynthons of hydrogen bonding have been identified in the studied crystals, and their relative stability has been ranked in terms of total interaction energies. The thermodynamics of the cocrystallization reactions has been systematically investigated using two independent experimental techniques, namely solution calorimetry and phase solubility diagram, which allowed us to assess both the enthalpic and the entropic contributions to the cocrystal formation driving force. The pH-solubility behavior of the cocrystals has been investigated at different pH values using eutectic concentrations of the components. Although all of the cocrystals reported here were found to be more soluble than the parent drug, their advantage in thermodynamic solubility did not translate into enhanced dissolution performance due to a rapid solution-mediated phase transformation in aqueous media. In addition, the effect of cocrystallization on other pharmaceutically relevant properties of nitrofurantoin, including photostability and membrane permeability, has been considered and analyzed.

Sir, A wide spectrum of drugs can induce headache, which is in fact one of the most common adverse drug events . Although headache is usually a nonserious, unwanted effect, it could be difficult to quickly and correctly diagnose, leading to repeated medical consultations, prescription of laboratory or instrumental examinations, and even hospitalization [1]. The International Headache Classification (IHC), in Chapter 8, includes these secondary headaches as adverse reactions to drugs . Whereas some drug-related headaches are well characterized, others lack specific and accurate definition [1]. We present a patient experiencing cluster-like attacks after nitrofurantoin consumption.

The purpose of this study was to analyze the various risk factors for urosepsis following percutaneous nephrolithotomy (PNL) and to study the role of 1-week nitrofurantoin before PNL in reducing the risk of urosepsis. All patients undergoing PNL from April 2007 to November 2008 were prospectively included and grouped into four cohorts according to the following inclusion criteria: group A: stones B 2.5 cm, no hydronephrosis, sterile urine; group B: diabetes mellitus, serum creatinine [ 2 mg/dl, positive urine culture, stag horn stones, presence of nephrostomy or simultaneous bilateral PNL; group C: stones C 2.5 cm and/or hydronephrosis, sterile urine; group D: similar to group C, but received nitrofurantoin 100 mg bid for 7 days before operation. Preoperative urine culture, intraoperative renal pelvic urine culture and stone cultures were obtained. Fever [ 380°C and leukocyte counts [ 12,000 were considered as systemic inflammatory response syndrome (SIRS). Endotoxemia was assessed in serum samples. A total of 205 patients were included in the study and grouped into four cohorts as group A (n = 50), group B (n = 54), group C (n = 53) and group D (n = 48). Overall 23% patients had positive renal pelvic urine and/or stone culture, 25% had endotoxemia and 34% developed SIRS. Female gender, chronic renal failure, anemia, hydronephrosis, stones larger than 2.5 cm and prolonged surgery were found to be risk factors associated with urosepsis. Nitrofurantoin prophylaxis resulted in decreased culture positivity (30.2 vs. 8.3%, odds ratio 0.36, p = 0.087), endotoxemia (41.9 vs. 17.5%, odds ratio 0.22, p = 0.001) and SIRS (49 vs. 19%, odds ratio 0.31, p = 0.01). In conclusion, female gender, chronic renal failure, anemia, hydronephrosis, stones larger than 2.5 cm and prolonged surgery were risk factors for urosepsis. Nitrofurantoin is beneficial in the prevention of endotoxemia and urosepsis especially in patients with larger stones and hydronephrosis.

The influence of route of administration on the absolute bioavailability and GI tract absorption of nitrofurantoin was investigated in rabbits. The disposition of nitrofurantoin was described by a one-compartment model with simultaneous first-order and Michaelis-Menten type elimination kinetics, and bioavailability was estimated by nonlinear assessment. The plasma levels following oral administration were significantly lower than those after intravenous administration, and absolute Fvalues for oral administration were approximately 0.3. However, Fvalues following intraduodenal administration and portal vein infusion were nearly unity, and it was concluded that the reduction of bioavailability following oral administration could not be attributed to metabolism by intestinal microflora or to the hepatic first-pass effect. Thus, reduction of Fvalues following oral administration is probably due to gastric degradation of the drug. The effects of factors influencing bioavailability, such as water volume taken with the drug, change of gastric emptying rate and effect of particle size, were also investigated. Increase of volume of water administered tended to improve the bioavailability, and a particle size dependency was also observed.

It is important to determine the toxicity of compounds and co-solvents that are used in cell monolayer permeability studies to increase confidence in the results obtained from these in vitro experiments. This study was designed to evaluate the cytotoxicity of new nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA) in Caco-2 cells to select analogues for further in vitro permeability analyses. In this study, nitrofurantoin and nifuroxazide, in addition to 6 furanic and 6 thiophenic nifuroxazide derivatives were tested at 2, 4, 6, 8 and 10 μg/mL. In vitro cytotoxicity assays were performed according to the MTT (methyl tetrazolium) assay protocol described in ISO 10993-5. The viability of treated Caco-2 cells was greater than 83% for all tested nitrofurantoin concentrations, while those treated with nifuroxazide at 2, 4 and 6 μg/mL had viabilities greater than 70%. Treatment with the nifuroxazide analogues resulted in viability va...

Objective: To investigate the role of skin biopsy in nitrofurantoin peripheral neuropathy. Design: We describe the clinical features and skin biopsies of 2 cases of non-length-dependent smallfiber neuropathy/ganglionopathy attributable to nitrofurantoin.

Objective: To investigate the role of skin biopsy in nitrofurantoin peripheral neuropathy. Design: We describe the clinical features and skin biopsies of 2 cases of non-length-dependent smallfiber neuropathy/ganglionopathy attributable to nitrofurantoin.

More than 20 medications are associated with the organizing pneumonia, and, specifically, bronchiolitis obliterans organizing pneumonia (BOOP) lesion . Several classes of medications cause the BOOP reaction, including antimicrobials, anticancer agents, cardiac agents, and anti-inflammatory agents [1 -4]. The BOOP reaction represents an inflammatory response of the lung, and, therefore, is generally reversible by drug cessation or corticosteroid therapy. Organizing pneumonia is a general term that includes BOOP. This article uses the term BOOP because most reports specifically show BOOP as the medication reaction. The article includes a review of the clinical findings, radiographic abnormalities, physiologic findings, and management of druginduced BOOP. This article is arranged by category and name of the drug because the clinician will be presented with a patient who develops respiratory symptoms while taking a certain medication.

Within the EU, the use of nitrofurans is prohibited in food production animals. For this reason detection of these compounds in feedingstuffs, at whatever limit, constitutes an offence under EU legislation. This detection generally involves the use of analytical methods with limits of quantification lowers than 1 mg kg −1 . These procedures are unsuitable for the detection and confirmation of trace amounts of nitrofurans in feedingstuffs due to contamination. It is well known that very low concentrations of these compounds can be the source of residues of nitrofuran metabolites in meat and other edible products obtained from animals consuming the contaminated feed. The present multi-compound method was capable of measuring very low concentrations of nitrofurantoin (NFT), nitrofurazone (NFZ), furazolidone (FZD) and furaltadone (FTD) in animal feed using nifuroxazide (NXZ) as internal standard. Following ethyl acetate extraction at mild alkaline conditions and purification on NH 2 column, the nitrofurans are determined using liquid chromatography with photodiode-array detection (LC-DAD). It was observed a CC␣ ranged from 50 to 100 g kg −1 . The liquid chromatography-tandem mass spectrometric (LC-MS/MS) procedure was used to confirm the identity of the suspected presence of any of the nitrofuran compounds.

There have been few recent reviews of the nitrofurans in the literature, and none include recently available data on the use of nitrofurazone (nitrofural) in the prevention of catheter-associated urinary tract infection (CAUTI). Nitrofurazone and nitrofurantoin are the only nitrofurans that have become established in clinical use in the 20th century. These 2 nitrofurans have remained clinically useful against a wide spectrum of Gram-positive and Gram-negative bacteria, including many strains of common urinary tract pathogens. Today, the primary use of nitrofurantoin is as an oral antibacterial treatment for genitourinary infections. Nitrofurazone is primarily used as a topical antibacterial agent in burns and skin grafts and recently was approved for the prophylaxis of CAUTI. The recent development of a nitrofurazone-impregnated catheter as a novel modality in the prevention of CAUTI reflects a renewed interest in the effectiveness of nitrofurans. In an era when concern about bacterial resistance to many anti-infective agents is growing, the nitrofurans have continued to be active against organisms that have developed resistance to antibacterials. The presence of multiple mechanisms of action for the nitrofurans might be expected to reduce the ability of bacteria to develop resistance. Considering that an emergence of resistance to the nitrofurans has not appreciably occurred after several decades of clinical use, the nitrofurans may be unique among common antibacterial agents in this regard.

The aim of this study was to determine the distribution of uropathogens isolated from outpatients living in South Croatia and the in vitro susceptibility of these organisms to antimicrobial agents. Of 5080 enrolled uropathogen isolates, 82.28% isolates were Gram-negative, the most frequent isolates being Escherichia coli (62.62%), enterococci (10.18%), Proteus mirabilis (5.31%), Streptococcus agalactiae (3.84%), Staphylococcus spp. (3.70%), Pseudomonas spp. (3.46%), Klebsiella spp. (2.38%). The E. coli resistance rate was 42.17% to amoxycillin, 20.59% to trimethoprim-sulphamethoxazole and 6.09% to norfloxacin. Almost all Klebsiella spp. isolates were resistant to amoxycillin and the resistance rate to trimethoprim-sulphamethoxazole was over 20%, and 14.15% to the fluoroquinolones. A high methicillin-resistance rate was found among S. aureus (61.22%) and coagulase negative staphylococci (41.48).

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. 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. 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. 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 th...

Uropathogenic E. coli CTX-M a b s t r a c t Carbon monoxide (CO) releasing molecules (CO-RMs) have been shown to inhibit growth of commensal Escherichia coli (E. coli). In the present study we examined the effect of CORM-2 on uropathogenic E. coli (UPEC) that produces extended-spectrum b-lactamase (ESBL). Viability experiments showed that CORM-2 inhibited the growth of several different ESBL-producing UPEC isolates and that 500 mM CORM-2 had a bactericidal effect within 4 h. The bactericidal effect of CORM-2 was significantly more pronounced than the effect of the antibiotic nitrofurantoin. CORM-2 demonstrated a low level of cytotoxicity in eukaryotic cells (human bladder epithelial cell line 5637) at the concentrations and time-points where the antibacterial effect was obtained. Real-time RT-PCR studies of different virulence genes showed that the expression of capsule group II kpsMT II and serum resistance traT was reduced and that some genes encoding iron acquisition systems were altered by CORM-2. Our results demonstrate that CORM-2 has a fast bactericidal effect against multiresistant ESBL-producing UPEC isolates, and also identify some putative UPEC virulence factors as targets for CORM-2. CO-RMs may be candidate drugs for further studies in the field of finding new therapeutic approaches for treatment of uropathogenic ESBLproducing E. coli.

A new, simple and sensitive spectrofluorimetric method has been developed for the determination of pregabalin (PG) in capsules. The method is based on the reaction between pregabalin and fluorescamine in borate buffer solution of pH 10 to give a highly fluorescent derivative that is measured at 487 nm after excitation at 390 nm. The different experimental parameters affecting the development and stability of the reaction product were carefully studied and optimized. The fluorescence intensity concentration plot was rectilinear over the range of 0.01-0.3 mg mL -1 with a lower detection limit of 0.0017 mg mL -1 and limit of quantitation of 0.005 mg mL -1 . The developed method was successfully applied to the analysis of the drug in its commercial capsules. The mean percentage recovery of PG in its capsule was 99.93Ϯ1.24 (n = 3). Statistical comparison of the results with those of the comparison method revealed good agreement and proved that there was no significant difference in the accuracy and precision of the two methods. A proposed reaction pathway was postulated.

The influence of the boron-doping levels in boron-doped diamond film electrodes on the electrochemical response of nitrofurantoin (NFT) and the development of an electroanalytical procedure for NFT determination were investigated. The investigations were carried out using the techniques of cyclic voltammetry and square wave voltammetry on diamond film electrodes with different boron-doping levels (i.e., 5000, 10,000 and 20,000 mg L −1 ). The level of boron-doping in the diamond film electrodes influenced the electrochemical reduction of NFT. The appropriate cyclic voltammetric response of NFT was obtained with Britton-Robinson buffer at pH 4 and for diamond films doped with 10,000 and 20,000 mg L −1 of boron. These two films were selected for the development of the electroanalytical procedure. The use of square wave voltammetry with the optimized parameters demonstrated a good linear relationship between the peak current and the NFT concentration for a wide range of concentration. The lower limit of detection for the electrodes doped with 10,000 and 20,000 mg L −1 of boron were 2.69 × 10 −8 mol L −1 (6.40 g L −1 ) and 8.15 × 10 −9 mol L −1 (1.94 g L −1 ), respectively, while the lower limits of quantification were 8.96 × 10 −8 mol L −1 (21.33 g L −1 ) and 2.72 × 10 −8 mol L −1 (6.47 g L −1 ), respectively. The applicability of the proposed procedure was tested using a commercial pharmaceutical formulation of NFT, and the results were compared with the procedure recommended by the British Pharmacopeia. The proposed procedure was sensitive, accurate and precise for analysis of NFT and did not require complex preparations or renovations of the electrode surface. This presents the advantage of eliminating mercury waste and minimizing the adsorptive problems related to the use of other electrodic solid surfaces.

Purpose: We evaluated the effectiveness of combining behavioral therapy, pharmacologic therapy and endoscopic hydrodistension for treating painful bladder syndrome / interstitial cystitis (PBS/IC). Materials and Methods: Twenty-five patients with PBS/IC were prospectively enrolled in a pilot multimodal behavioral, pharmacologic and endoscopic treatment protocol. Behavioral modification included diet recommendations, fluid restriction to 64 oz. /day, progressive timed voiding and Kegel exercises. Oral pharmacologic therapy consisted of daily doses of macrodantin 100 mg, hydroxyzine 10-20 mg and urised 4 tablets. Patients underwent endoscopic bladder hydrodistention under anesthesia at least 2 weeks after protocol enrollment. Behavioral and pharmacological treatments were continued after the hydrodistention. O'Leary-Sant questionnaire scores were recorded before starting the protocol, after pharmacologic/behavioral therapy, 2 months post-hydrodistension, and at scheduled follow-up. Results: Eighteen patients (72%) completed the pilot multimodal treatment protocol and were followed for a mean of 10.2 months. All patients were female with a median age of 36.3 years and had mean bladder capacity under anesthesia of 836 milliliters. Mean O'Leary-Sant symptom index scores for baseline symptoms, after behavioral/pharmacologic treatment, post-hydrodistension and during follow up were 12.5, 8.6, 7.0, and 6.7 (p < 0.05). Mean O'Leary-Sant problem index scores for baseline, after behavioral/pharmacologic treatment, post-hydrodistention and during follow up were 12.7, 8.9, 6.7, and 7.7 (p < 0.05). Conclusion: Our pilot multimodal protocol of behavioral modification, pharmacologic therapy and endoscopic hydrodistention demonstrated a significant progressive improvement in PBS/IC quality of life scores, compared to a pre-treatment baseline. These results should be validated in a larger, placebo controlled trial.

Background: There is paucity of information regarding the epidemiology of Escherichia coli O157: H7 in developing countries. In this study, we investigated the occurrence of E. coli O157: H7 associated with beef cattle at processing plants and at retail shops in Ethiopia. Methods: Various samples were collected from beef cattle at slaughter/processing plants, carcass at retail shops and humans at health centers. E. coli O157: H7 was isolated, identified and characterized for antimicrobial resistance, using standard microbiological methods. Results: At the processing plants E. coli O157: H7 was detected in 1.89% of fecal, 0.81% of intestinal mucosal swab, 0.54% of skin swab and 0.54% of carcass internal swab samples. At retail shops it was detected in 0.8% of carcass and 0.8% of cutting board swab samples, while all samples from utensils, hands from workers, and fecal and stool samples were negative. All isolates were resistant to Amoxicillin, moderately resistant to Cefoxitine and Nitrofurantoins but susceptible to other antimicrobials tested. Conclusions: E. coli O157: H7 occurs at low prevalence in beef cattle, and the current sanitary dressing procedures in the processing plants and storage conditions in the retail shops are effective against E. coli O157: H7.

Thirty-minute perfusion of isolated rabbit lungs with a Krebs-Ringer bicarbonate buffer containing 420 @f paraquat (PQ) or nitrofurantoin (NF) resulted in increases in lung oxidized glutathione (GSSG) content of 589 and 2656%, respectively, over control levels. The degree of glutathione efflux was also increased with both agents, i.e. 77 and 238% above control leakage for PQ and NF respectively. The pulmonary toxicity of both compounds is known to be heightened by conditions of hyperoxia(O2). Ventilation of lungs with 95% Or-5% CO2 did not, in itself, significantly alter glutathione efflux, GSH or GSSG levels. However, ventilation with 95% 0r5% CO* increased lung GSSG levels in PQ-perfused lungs 225% over PQ-air-perfused lungs, a combined effect not observed with NF-02, wherein mean GSSG levels were only 72% of that observed with NF-air. Glutathione efflux in PQ-OZ-treated lungs declined somewhat (20%) compared to that observed with PQ-air, but a significant increase in the amount of glutathione efflux was seen with NF-Or-treated lungs, i.e. 120 and 310%, respectively, over that attributable to NF or O2 alone. Although the biochemical mechanisms of toxicity of these compounds are thought to be very similar, the disparate degree of GSH oxidation observed with equimolar levels of PQ and NF may indicate differences in reactivity towards glutathione and other lung s~~ydryl pools. The stim~ation of the oxidative effects of PQ and NF on lung GSH due to hyperoxic ventilation may be related to the reported 02 enhancement of their toxicity.

Nitrofurans belong to a group of synthetic broad spectrum antibacterial agents having a nitrofuran ring. Nitrofurantoin [NFT, 1-{(5-nitro-2-furyl)methylideneamino}imidazolidine-2,4-dione] is a nitro furan-derivative antibacterial agent, used in human and veterinary medicine (1, 2). In humans, it is widely used to treat urinary tract infections. NFT is effective against common urinary tract pathogens, including Escherichia coli, Enterococci, Kleb-

Objectives: The biological fitness cost of antibiotic resistance is a key parameter in determining the rate of appearance and spread of antibiotic-resistant bacteria. We identified mutations conferring nitrofurantoin resistance and examined their effect on the fitness of clinical Escherichia coli isolates.

The z-crystallin (ZCr) gene P1 of Arabidopsis thaliana, known to confer tolerance toward the oxidizing drug 1,1 H -azobis(N,N-dimethylformamide) (diamide) to yeast [Babiychuk, E., Kushnir, S., Belles-Boix, E., Van Montagu, M. & Inze Â, D. (1995) J. Biol. Chem. 270, 26224], was expressed in Escherichia coli to characterize biochemical properties of the P1-z-crystallin (P1-ZCr). Recombinant P1-ZCr, a noncovalent dimer, showed NADPH:quinone oxidoreductase activity with specificity to quinones similar to that of guinea-pig ZCr. P1-ZCr also catalyzed the divalent reduction of diamide to 1,2-bis(N,N-dimethylcarbamoyl)hydrazine, with a k cat comparable with that for quinones. Two other azodicarbonyl compounds also served as substrates of P1-ZCr. Guinea-pig ZCr, however, did not catalyze the azodicarbonyl reduction. Hence, plant ZCr is distinct from mammalian ZCr, and can be referred to as NADPH:azodicarbonyl/quinone reductase. The quinone-reducing reaction was accompanied by radical chain reactions to produce superoxide radicals, while the azodicarbonylreducing reaction was not. Specificity to NADPH, as judged by k cat /K m , was . 1000-fold higher than that to NADH both for quinones and diamide. N-Ethylmaleimide and p-chloromercuribenzoic acid inhibited both quinone-reducing and diamide-reducing activities. Both NADPH and NADP 1 suppressed the inhibition, but NADH did not, suggesting that sulfhydryl groups reside in the binding site for the phosphate group on the adenosine moiety of NADPH. The diamide-reducing activity of P1-ZCr accounts for the tolerance of P1-overexpressing yeast to diamide. Other possible physiological functions of P1-ZCr in plants are discussed.

To evaluate the role of nitrofurantoin (NFT) prophylaxis in a prospective randomized control study. Urosepsis is an important complication after percutaneous nephrolithotomy (PNL). Risk increases by around 4 times with larger stones and hydronephrosis (HDN). Patients with stones ≥2.5 cm and/or HDN and sterile urine undergoing PNL were randomized into 2 groups. Standard perioperative antibiotic prophylaxis was the same in both groups. One group received sustained-released NFT 100 mg b.i.d. for 7 days preoperatively, and the other did not. Preoperative urine, intraoperative renal pelvic urine, and stone cultures were obtained. Postoperative occurrence of SIRS was considered urosepsis after excluding other causes. Serum samples were collected immediately after PNL and stored at -20°C. Serum endotoxin was estimated using Limulus Amoebocyte Lysate gelation technique (Sigma Aldrich, Saint Louis, Missouri). The operating surgeons and the microbiologist were blinded to the group distribution. Of 101 patients, 48 received nitrofurantoin prophylaxis. Both groups were comparable for age, gender, stone burden, degree of HDN, duration of operation, and intraoperative blood loss. There was significantly low positive pelvic urine culture (0% vs 9.8%, RR 4.95, P = .001), positive stone culture (8.3% vs 30.2%, RR 3.64, P = .001), endotoxemia (17.5% vs 41.9%, OR 0.22, P = .016), and systemic inflammatory response system (19% vs 49%, OR 0.31, P = .01) in patients receiving NFT prophylaxis. Prophylaxis with NFT for a week before PNL is beneficial in the prevention of urosepsis and endotoxemia in patients with larger stones and HDN. NFT covers most of the urinary isolates and is preferred in areas of fluoroquinolone resistance.

Presentamos el caso de una mujer de 40 añ os diagnosticada de enfermedad pulmonar intersticial secundaria a la administració n cró nica de nitrofurantoína. A pesar de la grave desestructuració n de la arquitectura bronquiolar y una tomografía computarizada de tó rax que confirmó la presencia de panalizació n, la biopsia transbronquial mostró un patró n de neumonitis intersticial aguda-subaguda y el cuadro clínico y radioló gico se resolvió en el plazo de un mes tras la administració n de prednisona. Este caso pone de manifiesto que la enfermedad pulmonar inducida por nitrofurantoína puede llegar a ser una entidad benigna con respuesta favorable a los corticoides, incluso en el caso de que haya datos radioló gicos de fibrosis pulmonar establecida. La biopsia transbronquial podría ser una prueba ú til para evaluar la reversibilidad de las lesiones pulmonares asociadas a la nitrofurantoína.

Empirical treatment of uncomplicated urinary tract infections (UTIs) in women should be based on local susceptibility data. We aimed to generate regional and provincial cumulative antibiograms combining data from different laboratory information systems and determine the impact of basic patient characteristics on susceptibility results. All positive urine samples for Escherichia coli obtained from women aged 18-65 years old in outpatient settings between 1 April 2010 and 31 March 2015 from four hospitals in Quebec, Canada, were included. The cumulative antibiogram for ciprofloxacin, nitrofurantoin and trimethoprim/sulfamethoxazole was calculated. A clinically significant difference in susceptibility profile was defined as factor(s) that lowered the susceptibility proportion below 80%. A total of 36 293 positive urine cultures were analysed. In the last year of the study, the proportion of susceptibility for ciprofloxacin, nitrofurantoin and trimethoprim/sulfamethoxazole was 90.3%, 9...