Nitrofurantoin

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...

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...

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.

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...

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...

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.

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...