Concomitant pulmonary and hepatic toxicity secondary to nitrofurantoin: a case report

<p>Abstract</p> <p>Background</p> <p>Concomitant pulmonary and hepatic toxicity secondary to nitrofurantoin is a rare but serious complication of the use of Nitrofurantoin.</p> <p>Case presentation</p> <p>A 72 year old woman taking Nitrofurantoin for recurrent urinary sepsis presenting with breathlessness abdominal discomfort and abnormal liver function tests is described. Drug toxicity secondary to Nitrofurantoin was diagnosed. Cessation of the drug and a course of steroids markedly improved her condition.</p> <p>Discussion</p> <p>We review the drug reactions associated with Nitrofurantoin and suggest an alternative treatment strategy for recurrent urinary sepsis.</p> <p>Conclusion</p> <p>Adverse drug reactions are an important cause of concomitant lung and liver toxicity and the mainstay of treatment is drug withdrawal.</p

The structure of the PapD-PapGII pilin complex reveals an open and flexible P5 pocket

P pili are hairlike polymeric structures that mediate binding of uropathogenic Escherichia coli to the surface of the kidney via the PapG adhesin at their tips. PapG is composed of two domains: a lectin domain at the tip of the pilus followed by a pilin domain that comprises the initial polymerizing subunit of the 1,000-plus-subunit heteropolymeric pilus fiber. Prior to assembly, periplasmic pilin domains bind to a chaperone, PapD. PapD mediates donor strand complementation, in which a beta strand of PapD temporarily completes the pilin domain's fold, preventing premature, nonproductive interactions with other pilin subunits and facilitating subunit folding. Chaperone-subunit complexes are delivered to the outer membrane usher where donor strand exchange (DSE) replaces PapD's donated beta strand with an amino-terminal extension on the next incoming pilin subunit. This occurs via a zip-in-zip-out mechanism that initiates at a relatively accessible hydrophobic space termed the P5 pocket on the terminally incorporated pilus subunit. Here, we solve the structure of PapD in complex with the pilin domain of isoform II of PapG (PapGIIp). Our data revealed that PapGIIp adopts an immunoglobulin fold with a missing seventh strand, complemented in parallel by the G1 PapD strand, typical of pilin subunits. Comparisons with other chaperone-pilin complexes indicated that the interactive surfaces are highly conserved. Interestingly, the PapGIIp P5 pocket was in an open conformation, which, as molecular dynamics simulations revealed, switches between an open and a closed conformation due to the flexibility of the surrounding loops. Our study reveals the structural details of the DSE mechanism

Urinary tract infections in healthy women: a revolution in management?

<p>Abstract</p> <p>Background</p> <p>Urinary infection in otherwise healthy women has largely been a straightforward matter of diagnosis by identifying bacteria in the urine, and then cure by appropriate antibiotics. Recent research has shown this to be over-simplified. Evaluation of methods of self-management of symptoms has been neglected.</p> <p>Discussion</p> <p>Firstly trial data show that women with what used to called 'urethral syndrome' (urinary symptoms but sterile urine) obtain relief from antibiotics. Other trial data have shown a surprisingly large placebo effect from the resolution of symptoms among women who feel their care has been 'positive'. In addition, data published this month in <it>BMC Medicine </it>show that non-steroidal anti-inflammatory (NSAID) drugs provide symptom relief to women with conventional infections (positive urine bacteriology) as much as antibiotics.</p> <p>Conclusions</p> <p>These recent findings provide an opportunity to consider how clinicians might change practice, and sets a new research agenda. We need to know (1) whether the effect of NSAIDs is replicable; (2) why some women in previous trials have had more symptoms if not treated with antibiotics sooner; (3) whether NSAIDs and antibiotics have an additive effect on relieving symptoms; (4) how we can harness the placebo effect better to assist out patients with this distressing and common complaint.</p> <p>See research article <url>http://www.biomedcentral.com/1741-7015/8/30</url></p

Viunalikeviruses are environmentally common agents of horizontal gene transfer in pathogens and biocontrol bacteria.

Bacteriophages have been used as natural biocontrol and therapeutic agents, but also as biotechnological tools for bacterial engineering. We showed recently that the transducing bacteriophage ϕMAM1 is a ViI-like phage and a member of the new genus, 'Viunalikevirus'. Here, we show that four additional ViI-like phages and three new environmentally isolated viunalikeviruses, all infecting plant and human pathogens, are very efficient generalised transducers capable of transducing chromosomal markers at frequencies of up to 10(-4) transductants per plaque-forming unit. We also demonstrate the interstrain transduction of plasmids and chromosomal markers, including genes involved in anabolism, genes for virulence and genes encoding secondary metabolites involved in biocontrol. We propose that all viunalikeviruses are likely to perform efficient horizontal gene transfer. Viunalikeviruses therefore represent useful agents for functional genomics and bacterial engineering, and for chemical and synthetic biology studies, but could be viewed as inappropriate choices for phage therapy.This research was supported by the EU Marie-Curie Intra-European Fellowship for Career Development (FP7- PEOPLE-2011-IEF) grant number 298003.This is the version of record of the article "Viunalikeviruses are environmentally common agents of horizontal gene transfer in pathogens and biocontrol bacteria" published in ISME Journal on August 2104 under the NPG Open Access option. The published version of record is available on the journal website at http://dx.doi.org/10.1038/ismej.2014.15

Asymptomatic bacteriuria in sickle cell disease: a cross-sectional study

BACKGROUND: It is known that there is significant morbidity associated with urinary tract infection and with renal dysfunction in sickle cell disease (SCD). However, it is not known if there are potential adverse outcomes associated with asymptomatic bacteriuria (ASB) infections in sickle cell disease if left untreated. This study was undertaken to determine the prevalence of ASB, in a cohort of patients with SCD. METHODS: This is a cross-sectional study of patients in the Jamaican Sickle Cell Cohort. Aseptically collected mid-stream urine (MSU) samples were obtained from 266 patients for urinalysis, culture and sensitivity analysis. Proteinuria was measured by urine dipsticks. Individuals with abnormal urine culture results had repeat urine culture. Serum creatinine was measured and steady state haematology and uric acid concentrations were obtained from clinical records. This was completed at a primary care health clinic dedicated to sickle cell diseases in Kingston, Jamaica. There were 133 males and 133 females in the sample studied. The mean age (mean ± sd) of participants was 26.6 ± 2.5 years. The main outcome measures were the culture of ≥ 10(5 )colony forming units of a urinary tract pathogen per milliliter of urine from a MSU specimen on a single occasion (probable ASB) or on consecutive occasions (confirmed ASB). RESULTS: Of the 266 urines collected, 234 were sterile and 29 had significant bacteriuria yielding a prevalence of probable ASB of 10.9% (29/266). Fourteen patients had confirmed ASB (prevalence 5.3%) of which 13 had pyuria. Controlling for genotype, females were 14.7 times more likely to have confirmed ASB compared to males (95%CI 1.8 to 121.0). The number of recorded visits for symptomatic UTI was increased by a factor of 2.5 (95% CI 1.4 to 4.5, p < 0.005) but serum creatinine, uric acid and haematology values were not different in patients with confirmed ASB compared with those with sterile urine. There was no association with history of gram negative sepsis. CONCLUSION: ASB is a significant problem in individuals with SCD and may be the source of pathogens in UTI. However, further research is needed to determine the clinical significance of ASB in SCD

Clinical Validation of Integrated Nucleic Acid and Protein Detection on an Electrochemical Biosensor Array for Urinary Tract Infection Diagnosis

BACKGROUND: Urinary tract infection (UTI) is a common infection that poses a substantial healthcare burden, yet its definitive diagnosis can be challenging. There is a need for a rapid, sensitive and reliable analytical method that could allow early detection of UTI and reduce unnecessary antibiotics. Pathogen identification along with quantitative detection of lactoferrin, a measure of pyuria, may provide useful information towards the overall diagnosis of UTI. Here, we report an integrated biosensor platform capable of simultaneous pathogen identification and detection of urinary biomarker that could aid the effectiveness of the treatment and clinical management. METHODOLOGY/PRINCIPAL FINDINGS: The integrated pathogen 16S rRNA and host lactoferrin detection using the biosensor array was performed on 113 clinical urine samples collected from patients at risk for complicated UTI. For pathogen detection, the biosensor used sandwich hybridization of capture and detector oligonucleotides to the target analyte, bacterial 16S rRNA. For detection of the protein biomarker, the biosensor used an analogous electrochemical sandwich assay based on capture and detector antibodies. For this assay, a set of oligonucleotide probes optimized for hybridization at 37°C to facilitate integration with the immunoassay was developed. This probe set targeted common uropathogens including E. coli, P. mirabilis, P. aeruginosa and Enterococcus spp. as well as less common uropathogens including Serratia, Providencia, Morganella and Staphylococcus spp. The biosensor assay for pathogen detection had a specificity of 97% and a sensitivity of 89%. A significant correlation was found between LTF concentration measured by the biosensor and WBC and leukocyte esterase (p<0.001 for both). CONCLUSION/SIGNIFICANCE: We successfully demonstrate simultaneous detection of nucleic acid and host immune marker on a single biosensor array in clinical samples. This platform can be used for multiplexed detection of nucleic acid and protein as the next generation of urinary tract infection diagnostics

Treatment Duration of Febrile Urinary Tract Infections

Although febrile urinary tract infections (UTIs) are relatively common in adults, data on optimal treatment duration are limited. Randomized controlled trials specifically addressing the elderly and patients with comorbidities have not been performed. This review highlights current available evidence. Premenopausal, non-pregnant women without comorbidities can be treated with a 5–7 day regimen of fluoroquinolones in countries with low levels of fluoroquinolone resistance, or, if proven susceptible, with 14 days of trimethoprim-sulfamethoxazole. Oral β-lactams are less effective compared with fluoroquinolones and trimethoprim-sulfamethoxazole. In men with mild to moderate febrile UTI, a 2-week regimen of an oral fluoroquinolone is likely sufficient. Although data are limited, this possibly holds even in the elderly patients with comorbidities or bacteremia

A hospital-site controlled intervention using audit and feedback to implement guidelines concerning inappropriate treatment of catheter-associated asymptomatic bacteriuria

<p>Abstract</p> <p>Background</p> <p>Catheter-associated urinary tract infection (CAUTI) is one of the most common hospital-acquired infections. However, many cases treated as hospital-acquired CAUTI are actually asymptomatic bacteriuria (ABU). Evidence-based guidelines recommend that providers neither screen for nor treat ABU in most catheterized patients, but there is a significant gap between these guidelines and clinical practice. Our objectives are (1) to evaluate the effectiveness of an audit and feedback intervention for increasing guideline-concordant care concerning catheter-associated ABU and (2) to measure improvements in healthcare providers' knowledge of and attitudes toward the practice guidelines associated with the intervention.</p> <p>Methods/Design</p> <p>The study uses a controlled pre/post design to test an intervention using audit and feedback of healthcare providers to improve their compliance with ABU guidelines. The intervention and the control sites are two VA hospitals. For objective 1 we will review medical records to measure the clinical outcomes of inappropriate screening for and treatment of catheter-associated ABU. For objective 2 we will survey providers' knowledge and attitudes. Three phases of our protocol are proposed: the first 12-month phase will involve observation of the baseline incidence of inappropriate screening for and treatment of ABU at both sites. This surveillance for clinical outcomes will continue at both sites throughout the study. Phase 2 consists of 12 months of individualized audit and feedback at the intervention site and guidelines distribution at both sites. The third phase, also over 12 months, will provide unit-level feedback at the intervention site to assess sustainability. Healthcare providers at the intervention site during phase 2 and at both sites during phase 3 will complete pre/post surveys of awareness and familiarity (knowledge), as well as of acceptance and outcome expectancy (attitudes) regarding the relevant practice guidelines.</p> <p>Discussion</p> <p>Our proposal to bring clinical practice in line with published guidelines has significant potential to decrease overdiagnosis of CAUTI and associated inappropriate antibiotic use. Our study will also provide information about how to maximize effectiveness of audit and feedback to achieve guideline adherence in the inpatient setting.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01052545">NCT01052545</a></p