Nitrofurantoin: the return of an old friend in the wake of growing resistance

OBJECTIVE

To re‐evaluate the first‐ and second‐line therapies for treating uncomplicated urinary tract infection (UTI), as although fluoroquinolones are commonly used for this purpose, its level of use is thought to be inappropriately excessive and will eventually have a detrimental impact; thus we hypothesise that nitrofurantoin might be the best choice for this indication, due to its low frequency of use and its high susceptibility rate in common UTI pathogens.

MATERIALS AND METHODS

We retrospectively analysed antimicrobial susceptibility patterns of urinary isolates from 2003 to 2007, taken from a community‐based institutional hospital in Brooklyn, NY, USA.

RESULTS

In all, 10 417 cultures grew Escherichia coli from 2003 to 2007. Overall, from 2003 to 2007, 95.6% of E. coli urine isolates were susceptible to nitrofurantoin, with an average 2.3% resistance rate. By contrast, E. coli uropathogens had a mean 75.6% and 75.9% susceptibility and 24.2% and 24% resistance rate to both ciprofloxacin and levofloxacin, respectively. Co‐trimoxazole (trimethoprim/sulfamethoxazole; ‘TMP/SMX’) had a mean 29% resistance rate to E. coli over the same 5‐year period.

CONCLUSIONS

We consider that nitrofurantoin is a good fluoroquinolone‐sparing alternative to co‐trimoxazole; this study shows that nitrofurantoin is bactericidal to a mean of 95% of E. coli UTIs. Nitrofurantoin also has a resistance rate of 2.3%, by contrast to the quinolones (ciprofloxacin and levofloxacin), with resistant rates of ≈24%, and Co‐trimoxazole, with a resistant rate of 29%. Nitrofurantoin is an acceptable treatment for uncomplicated UTIs and should now be considered the first‐line treatment. A reconsideration of UTI treatment guidelines might now be appropriate.     

Relationship between energetic stress and pro-apoptotic/cytoprotective kinase mechanisms in intestinal preservation

BACKGROUND: A recent study from our laboratory documented significant improvements in post-transplant viability in an experimental model of intestinal transplantation when a novel, nutrient-rich preservation solution was used during cold storage. The current study investigated the relationship between energetic/oxidative stress responses and fundamental kinase signaling events during the period of organ storage. This relationship may be a key factor contributing to improved graft viability after storage in a nutrient-rich preservation solution. METHODS: Rat small intestine was harvested and flushed intraluminally with University of Wisconsin (UW) solution or an amino acid-rich (AA) solution as follows: Group 1, no luminal flush (clinical control); Group 2, luminal UW solution; Group 3, luminal AA solution. Energetics (ATP, total adenylates), oxidative stress (malondialdehyde), histology, and MAPK (P38, JNK, ERK)/AMPK/Caspase-3 were assessed throughout 12-hour cold storage. RESULTS: P38 and JNK were upregulated strongly in Group 2 after 1- and 12-hour storage. Group 3 exhibited a delayed activation and subsequent downregulation of these pre-apoptotic signals. Between 6 to 12 hours, a strong upregulation of ERK was observed in Group 3. AMPK downregulation correlated with a reduction in AMP/ATP ratio, ERK upregulation, and P38/JNK downregulation in Group 3. After 12-hour storage, histology indicated superior preservation of mucosal architecture in Group 3 tissues. CONCLUSIONS: A nutrient-rich preservation solution abrogates pre-apoptotic signaling (JNK and P38) and upregulates cytoprotective signals (ERK). Our data support the concept of a concerted effort facilitating cellular protection in response to ischemic stress.     

Do mitochondrial DNA haplogroups play a role in susceptibility to tuberculosis?

BACKGROUND AND OBJECTIVES: Mitochondrial DNA has a unique role in ATP production and subsequent mitochondrial reactive oxygen species (ROS) production in eukaryotic cells and there is a potential role for ROS and oxygen burst against Mycobacterium tuberculosis, an intracellular pathogen. This study aimed to determine whether the frequency of different mitochondrial haplogroups was significantly different in patients with tuberculosis (TB) compared with a normal population. METHODS: Mitochondrial DNA haplogroups M, N, J and K were studied by PCR-restriction fragment length polymorphism and sequencing. Cases were 54 patients with confirmed smear positive pulmonary TB. Controls were 256 healthy persons. RESULTS: There were no statistically significant differences between those with TB and the control group. CONCLUSIONS: There was no statistically significant association between mtDNA haplogroups and the presence of TB infection.     

Progressive CAG expansion in the brain of a novel R6/1-89Q mouse model of Huntington's disease with delayed phenotypic onset

Transgenic models representing Huntington's disease (HD) have proved useful for understanding the cascade of molecular events leading to the disease. We report an initial characterisation of a novel transgenic mouse model derived from a spontaneous truncation event within the R6/1 transgene. The transgene is widely expressed, carries 89 CAG repeats and the animals exhibit a significantly milder neurological phenotype with delayed onset compared to R6/1. Moreover, we report evidence of progressive somatic CAG expansions in the brain starting at an early age before an overt phenotype has developed. This novel line shares a common genetic ancestry with R6/1, differing only in CAG repeat number, and therefore, provides an additional tool with which to examine early molecular and neurophysiological changes in HD.     

Effect of hypnosis on induction of local anaesthesia,pain perception,control of haemorrhage and anxiety during extraction of third molars: A case–control study

IntroductionSystemic conditions are considered limiting factors for surgical procedures under local anaesthesia in the oral cavity. All the pharmacological methods to control pain in patients have some disadvantages, such as side effects and extra costs for rehabilitation. Therefore, in such cases alternative treatment modalities are considered, such as hypnosis in dentistry. The aim of the present study was to evaluate the effect of hypnosis on haemorrhage, pain and anxiety during the extraction of third molars.Materials and methodsIn this case–control study, 24 female and male volunteers were included. The subjects had been referred to the Department of Oral and Maxillofacial Surgery, Kerman University of Medical Sciences, for extraction of third molars. Demographic data for all the subjects were recorded. Patients with chronic medical conditions were excluded. The patients were used as their own controls, with the third molars on one side being removed under hypnosis and on the opposite side under local anaesthetic.Hypnosis was induced by one of the two methods, either fixing the gaze on one point or Chiasson's technique; both these methods are appropriate for patients in the dental chair. The Spielberger State-Trait Anxiety Inventory was used to determine patient anxiety levels before hypnosis and anaesthesia. Pain was scored using VAS (visual analogue scale). After surgery the patient was asked to bite on a sterile gauze pad over the surgical site for 30 min when haemorrhage from the area was evaluated. If there was no haemorrhage the patient was discharged. If haemorrhage persisted, the gauze pad was left in place for another 30 min and the area was re-evaluated. Any active oozing from the area after 30 min was considered haemorrhage. Haemorrhage, anxiety and pain were compared between the two groups. Data was analyzed using the t-test, McNemar's test and Wilcoxon's signed rank test using SPSS 18 statistical software.ResultsTwenty-four patients were evaluated; there were 14 males (58.3%) and 10 females (41.7%). The mean age of the subjects was 24.1 ± 2.7 years (age range = 18–30 years). A total of 48 third molars were extracted. In each patient, one-third molar was extracted under hypnosis and the other under local anaesthesia. All the patients were in the ASA 1 category (normal) with no significant medical history.Of the subjects who underwent hypnosis, only two subjects (8.3%) reported pain after induction of hypnosis. In the local anaesthetic group, 8 subjects (33.3%) reported pain. There was a significant difference between the two groups. The results of the study showed that patients in the hypnosis group had less pain during the first few hours post-operatively. Anxiety scores in the two groups were very close to each other and no statistically significant differences were observed in general and when each person was compared with himself or herself. Pain intensity in the two groups at 5- and 12-h post-operatively exhibited significant differences. In the hypnosis group, 10 patients (41.7%) took analgesic medication; in the local anaesthesia group, 22 patients (91.7%) took the analgesic medication (P = 0.0001). In other words, patients reported less pain when they were under hypnosis.ConclusionThe results of the study showed that hypnosis can effectively reduce anxiety, haemorrhage and pain. More studies are necessary to collect data on the effect of hypnosis on oral and maxillofacial surgeries.