Anaerobic infections of the urinary tract: are they being missed?

Routine anaerobic culture of urine identified the urinary tract as the primary focus of sepsis in a postoperative patient with Bacteroides fragilis septicaemia. Specimens of urine from six other symptomatic patients grew > 10(8) cfu/litre of a Bacteroides species in pure growth. The significance of these isolates is discussed. Multipoint technology and the availability of anaerobic work stations have facilitated anaerobic culture and reduced its cost. The incorporation of anaerobic culture of urine into routine laboratory practice may be clinically valuable and should be considered.     

Improved high-performance liquid chromatography assay of doxorubicin: Detection of circulating aglycones in human plasma and comparison with thin-layer chromatography

Summary We compared doxorubicin and metabolite pharmacokinetic data obtained from thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) assay of plasma samples from six patients who had been treated with doxorubicin. Duplicate 1-ml samples were extracted with chloroform: isopropanol (1:1) and assayed using a sensitive HPLC system incorporating a dual pump gradient with tetrahydrofuran as the mobile phase and fluorescence detection. Duplicate 1-ml samples from the same specimens were assayed using a modification of a previously described TLC assay. Areas under the curve for doxorubicin by HPLC (3.36±2.30 M · h) and TLC (4.16±2.50 M · h) were not significantly different (P=0.5). Terminal half-life of doxorubicin by HPLC (28.0±6.98 h) and TLC (23.2±7.8) (P=0.29) and the calculated total-body clearances by HPLC (0.55±0.29 l/min) and TLC (0.45±0.23) (P=0.55) were not significantly different. Areas under the curve for doxorubicinol by HPLC (2.75±1.4 M · h) and TLC (2.53±7.1 M · h) (P=0.73) showed no significant differences. HPLC detected a mixed 7-deoxydoxorubicinol aglycone-doxorubicin aglycone peak, 7-deoxydoxorubicin aglycone, and two nonpolar, unidentified metabolites. TLC detected the following aglycone metabolites: doxorubicin aglycone, doxorubicinol aglycone, 7-deoxydoxorubicinol aglycone, an unidentified polar metabolite, and several unidentified nonpolar metabolites. From these data we conclude that HPLC and TLC detect concentrations of doxorubicin and doxorubicinol from human plasma equally well to concentrations of 7.0 nM (4 pmol injected doxorubicin). Aglycones do circulate in human plasma at concentrations above the detection limits of both assays. Doxorubicinol aglycone, which is detected by TLC but not by HPLC, may be formed from artifactual breakdown of doxorubicinol during TLC development. Unidentified nonpolar compounds seen on HPLC and TLC may represent further doxorubicin metabolism than previously described.     

Long-term follow-up of a sponge breast implant and review of the literature

A case of a woman who underwent removal of a breast implant consistent with a polyvinyl sponge contained within a polyethylene bag is described. The use of the polyvinyl alcohol sponge as a breast implant virtually ceased in the mid 1960s with the introduction of silicone gel breast prostheses. However, it is still possible that the plastic surgeon may encounter a patient with one of these sponge implants in place. Thus, it is important for the plastic surgeon to be aware of their existence, natural history, and potential late complications. In addition, since the removal of silicone from general use for augmentation mammaplasty, there have been intense efforts to identify new filler materials for use in breast implants. Polyvinyl alcohol has been considered a possible material. There is a paucity of information in the recent literature pertaining to the characteristics and use of polyvinyl alcohol sponge implants. Therefore, this report describes a patient treated 38 years following placement of this type of implant and reviews the literature.     

Postprandial factor VII metabolism: the effect of the R353Q and 10 bp polymorphisms

Elevated levels of coagulation factor VII activity (FVIIc) are associated with increased risk of CHD. FVIIc is strongly determined by two polymorphisms (R353Q and 0/10 base pairs (bp)) and plasma triacylglycerol (TAG) concentrations. The Q and 10 bp polymorphisms show strong linkage disequilibrium and have been associated with lower levels of fasting FVII, but there has been little investigation of the effect of these genotypes on the postprandial FVII metabolism. The present study demonstrated that fasting activated factor VII (FVIIa) and factor VII antigen (FVIIag) levels were significantly lower in the heterozygotes carrying the Q and 10 bp alleles (n 12), than in the R/0 bp homozygotes (n 12) (43.0 (SE 4.8) v. 23.9 (SE 6.5) mU/ml and 85.7 (SE 5.4) v. 71.6 (SE 7.5)% respectively). During postprandial lipaemia there was a significant increase in FVIIa in R/0 bp homozygotes but not in the heterozygotes carrying the Q and 10 bp alleles. The proportion of FVIIa (FVIIa:FVIIag) increased in the homozygotes but not in the heterozygotes (2.04 (SE 0.35) v. 1.20 (SE 0.26) respectively). Therefore possession of the relatively common Q and 10 bp alleles is not associated with postprandial activation of FVII, which may in turn have a protective effect against CHD.     

Complications Following Antidotal Use of Intravenous Lipid Emulsion Therapy

The primary objective is to identify and describe the complications associated with the use of intravenous lipid emulsion (ILE) therapy as an antidote for lipophilic drug toxicity. This study is a retrospective chart review of patients treated with ILE at two academic medical centers between 2005 and 2012. Based on previously reported complications, we hypothesized that pancreatitis, ARDS, and lipemia-induced laboratory interference might occur. Clinical definitions of these complications were defined a priori. Subjects treated with ILE who did not develop at least one complication were excluded. A total of nine patients were treated with ILE during the study period, six of whom experienced potential complications as a result of the ILE. Two patients developed pancreatitis, and four patients had lipemia-induced interference of interpretation of laboratory studies, despite ultracentrifugation. Laboratory interference precluded one patient from being an organ donor. Three patients developed ARDS; although temporally associated, a causal relationship between ILE and the development of ARDS cannot be clearly established. As ILE is increasingly used for less severe cases of drug toxicity, clinicians should be aware of potential complications associated with its use. A risk–benefit assessment for the use of ILE should be implemented on a case-by-case basis.     

Are conventional microbiological diagnostics sufficiently expedient in the era of rapid diagnostics? Evaluation of conventional microbiological diagnostics of orthopedic implant-associated infections (OIAI)

Background and purpose — In a time when rapid diagnostics are increasingly sought, conventional procedures for detection of microbes causing orthopedic implant-associated infections (OIAI) seem extensive and time-consuming, but how extensive are they? We assessed time to (a) pathogen identification, (b) antibiotic susceptibility patterns, and (c) targeted antibiotic treatment using conventional microbiological diagnostics of OIAI in a consecutive series of patients.Patients and methods — Consecutive patients aged ≥18 years undergoing first revision surgery for acute OIAI, including prosthetic joints, fracture, and osteotomy implants, in 2017–2018 at Akershus University Hospital (Ahus), Norway were included. Information regarding microbiological diagnostics and clinical data was collected retrospectively from the hospital’s diagnostic and clinical databases.Results — 123 patients fulfilled the inclusion criteria. Median time to pathogen identification was 2.5 days and to antibiotic treatment recommendations was 3.5 days. The most common pathogens were S. aureus (52%) and S. epidermidis (15%). Cultures were inconclusive in 11% of the patients. Of the 109 patients with culture-positive results, antibiotic treatment was changed in 66 (61%) patients within a median of 4 days (0–24) after the recommendation was given.Interpretation — Conventional microbiological diagnostics of OIAI is time-consuming, taking days of culturing. Same-day diagnostics would vastly improve treatment efficacy, but is dependent on rapid implementation by clinicians of the treatment recommendations given by the microbiologist.

The majority of orthopedic procedures include the use of implants, which increase the risk of infection due to the reduced number of bacteria needed to establish an infection (Zimmerli et al. 1982). Orthopedic implant-associated infections (OIAI) are infrequent per se, with an overall surgical site infection rate following implant surgery of 3% (Skråmm et al. 2012). However, the number of patients undergoing orthopedic implant surgery is high and increasing (Norwegian National Advisory Unit on Arthroplasty and Hip Fractures 2020).A microbiological diagnosis is vital for providing the best treatment, with regards to both surgical options and providing targeted and narrow-spectrum antimicrobial therapy (Beam and Osmon 2018). Today’s conventional diagnostics include microbiological culturing of 5 biopsies from each infected patient on several different media for at least 5 days dependent on growing and dividing bacteria (Bergh et al. 2011, Osmon et al. 2013). More rapid diagnostic tools are being developed, but with varying degrees of sensitivity and specificity (Bonanzinga et al. 2017, Jun and Jianghua 2018, Aamot et al. 2019).We assessed time to (a) pathogen identification, (b) antibiotic susceptibility patterns, and (c) targeted antibiotic treatment using conventional microbiological diagnostics of OIAI in a consecutive series of patients.     

Safety of aerosolized INS 365 in patients with mild to moderate cystic fibrosis: results of a phase I multi-center study

Cystic fibrosis (CF) is characterized by defective cystic fibrosis transmembrane regulator (CFTR) expression and function, associated with abnormal ion transport and mucociliary clearance, and clinical lung disease. Triphosphate nucleotides such as uridine-5'-triphosphate (UTP) and INS 365, may be useful for CF through actions, mediated via P2Y(2) extracellular receptors, on chloride and liquid secretion, and ciliary beat frequency. INS 365 may offer chemical stability advantages over UTP. In a randomized, double-blind, multicenter phase I study, we studied the safety and maximally tolerated dose of escalating, single doses of aerosolized INS 365, in adult and pediatric patients with mild to moderate CF lung disease (FEV(1) > or = 45% predicted). In four successive dose cohorts of adult patients (n = 12 per cohort, age > or = 18 years) and four successive pediatric dose cohorts (n = 12 per cohort, age 5-12 years), patients were randomized 3:1 active/placebo (0.9% saline) to evaluate doses of 20, 40, 80, and 100 mg INS 365 delivered by nebulizer (Pari Star ). Sputum was collected pre- and post-dosing to obtain preliminary results on clinical efficacy. After each dose cohort, a Data Safety Monitoring Committee (DSMC) reviewed the data. Forty-eight adult and 36 pediatric patients completed the protocol (up to 100 mg for adults, 80 mg for pediatric patients). The predominant adverse events were cough, wheezing, chest tightness, and a decrease in FEV(1) (occurring in 8/48 adults, and 5/36 pediatric patients), which occurred predominantly in the 80-mg and 100-mg dose cohorts. Though a few adult patients had a tendency to increase sputum production, there was little consistent effect noted on sputum production in this acute, single-dose study. The data suggest that aerosolized INS 365 is safe when delivered at single doses of up to 40 mg in adults and children with CF, but that higher doses are unlikely to be tolerated.     

Rapid tranquilization: An audit of Irish mental health nursing practice

Rapid tranquillization is a pharmacological intervention sometimes employed in mental health care for the management of acute behavioural disturbance. It is a form of restrictive practice, which, along with seclusion and restraint, is a conventional and controversial intervention in the therapeutic management of risk in mental health settings. This study surveyed mental health nurses practice in rapid tranquillization. A self‐report questionnaire was utilized which addressed aspects such as definitions of rapid tranquillization, presence of rapid tranquillization policy, types of incidents where it is used and postintervention monitoring. The results demonstrate that rapid tranquillization is an intervention used in the management of acute behavioural disturbance in various mental health settings in Ireland. Respondents showed a basic understanding of rapid tranquillization as an intervention; however, some areas reported not having a specific rapid tranquillization policy. There was some evidence of a variation in postrapid tranquillization monitoring of psychiatric/mental health and physical health. Service user debriefing following rapid tranquillization was reported to be common; however, the content of this was not elaborated on. In the light of variations in practice, specific training and the development of rapid tranquillization policies are recommended.     

Clostridium difficile and inflammatory bowel disease.

Stools from 109 patients with inflammatory bowel disease (13.4%) contained Clostridium difficile or its toxin, an incidence similar to the stools of 99 control patients with diarrhoea (11.9%), but significantly higher than the stools of 77 control patients with a normal bowel habit (1.4%). Sixty-six per cent of the diarrhoea controls, but only 11% of the inflammatory bowel disease patients, reported recent antibiotic use: however, 67% of inflammatory bowel disease patients were taking sulphasalazine. The presence of Cl difficile in the stool was not related to the clinical assessment of inflammatory bowel disease relapse, but it was related to hospital admission. During the one year study, 31 of the 109 patients (28%) with inflammatory bowel disease had one or more stool samples that were positive for Cl difficile.