Invasive Propionibacterium acnes infections in a non-selective patient cohort: clinical manifestations, management and outcome.

An increasing number of reports suggest that Propionibacterium acnes can cause serious invasive infections. Currently, only limited data exist regarding the spectrum of invasive P. acnes infections. We conducted a non-selective cohort study at a tertiary hospital in the UK over a 9-year-period (2003-2012) investigating clinical manifestations, risk factors, management, and outcome of invasive P. acnes infections. Forty-nine cases were identified; the majority were neurosurgical infections and orthopaedic infections (n = 28 and n = 15 respectively). Only 2 cases had no predisposing factors; all neurosurgical and 93.3 % of orthopaedic cases had a history of previous surgery and/or trauma. Foreign material was in situ at the infection site in 59.3 % and 80.0 % of neurosurgical and orthopaedic cases respectively. All neurosurgical and orthopaedic cases required one or more surgical interventions to treat P. acnes infection, with or without concomitant antibiotic therapy; the duration of antibiotic therapy was significantly longer in the group of orthopaedic cases (median 53 vs 19 days; p = 0.0025). All tested P. acnes isolates were susceptible to penicillin, ampicillin and chloramphenicol; only 1 was clindamycin-resistant. Neurosurgical and orthopaedic infections account for the majority of invasive P. acnes infections. Most cases have predisposing factors, including previous surgery and/or trauma; spontaneous infections are rare. Foreign material is commonly present at the site of infection, indicating that the pathogenesis of invasive P. acnes infections likely involves biofilm formation. Since invasive P. acnes infections are associated with considerable morbidity, further studies are needed to establish effective prevention and optimal treatment strategies.

Microbiological aspects of the UK National Institute for Health and Clinical Excellence (NICE) guidance on urinary tract infection in children.

The publication in August 2007 of the UK National Institute for Health and Clinical Excellence (NICE) guidance on urinary tract infection in children provided a fresh and useful review of the management of this condition. However, it has also resulted in some controversy. In particular, the advice to use urgent microscopy for rapid screening of urine in children >or=3 months but <3 years of age has presented practical problems for some laboratories in staffing this service out of hours. Further discussion between microbiologists, paediatricians and primary care doctors regarding this recommendation is required. In addition, the abandoning of routine antibiotic prophylaxis following a first-time urine infection has caused some debate. The evidence around these issues is reviewed, as well as the differences in the laboratory processing and interpretation of paediatric urines compared with urine specimens from adults. General measures to reduce the risk of recurrence are also discussed. As mentioned in the NICE guidance, microbiologists should continue to emphasize the basic principles, particularly the importance of obtaining an accurate diagnosis from a well-collected and well-transported urine specimen.

Compliance with hand hygiene in a genitourinary medicine department.

The ability to control hospital-acquired infections is highly dependent upon control of cross-contamination from health-care workers to patients, and from one anatomical area of the patient to another anatomical area. Hand hygiene has been demonstrated to be an essential prerequisite in preventing cross-contamination. Wearing gloves does not afford complete protection against cross-contamination. Hand hygiene includes handwashing between patients, the use of alcohol-based skin cleansers and changing or removing gloves between examining different anatomical sites. There are no previously published audits regarding compliance to hand hygiene in genitourinary (GU) medicine clinics. A validated observation tool was employed in this audit. Doctors and nurses were observed in clinical practice. The adherence to hand hygiene protocols was overall poor. Doctors were more likely to adhere to protocols than nurses (83.3% vs. 66%). However, techniques of glove removal were universally satisfactory. Strategies for improvement in hand hygiene are suggested. These include performance feedback and use of posters.

Leptin signalling in pancreatic islets and clonal insulin-secreting cells.

Leptin is a cytokine secreted from adipose tissue at a rate commensurate with the size of the body's fat stores. In addition to its anorectic and thermogenic central actions, leptin is known to act on peripheral tissues, including the pancreatic beta-cell where it inhibits insulin secretion and reduces insulin transcript levels. However, the role of leptin signalling through its full-length receptor, OB-Rb, in the beta-cell remains unclear. In the present study, we show that leptin activates a signal transducer and activator of transcription (STAT)3 signalling mechanism in pancreatic islets and in a rat model of the pancreatic beta-cell, RINm5F. Leptin induced DNA binding to a STAT consensus oligonucleotide and resulted in transcriptional activation from STAT reporter constructs in a manner consistent with STAT3 activation. Western blot analysis confirmed activation of STAT3 in RINm5F and isolated rat islets. Conditions that mimic increased metabolic activity resulted in attenuation of leptin-mediated STAT DNA binding but had no significant effect on STAT3 tyrosine phosphorylation in RINm5F cells. In addition, leptin activated the mitogen activated protein (MAP) kinase pathway in RINm5F cells. The present study provides a framework for OB-Rb signalling mechanisms in the programming of the beta-cell by leptin and suggests that increased metabolic activity may modulate this function.

Fatal infection associated with group C streptococci.

Serious infection caused by Lancefield group C streptococci is unusual in man. Two unrelated deaths associated with these organisms in a 55 year old woman who died after three days of diarrhoea and vomiting, and in a 65 old man who died after a week of non-specific symptoms, are presented. Post mortem examination showed septicaemia in the former and severe aortic stenosis with widespread septic emboli and probable meningitis in the latter. Lancefield group C streptococci were isolated from both cases. These organisms may be carried asymptomatically and usually cause disease in animals but cases of serious human infection have recently been described, mainly in elderly patients or those with other predisposing factors.

Evidence that the ability of imidazoline compounds to stimulate insulin secretion is not due to interaction with sigma receptors.

Recent studies have suggested that a variety of ion channels possess a binding site for ligands such as phencyclidine (PCP), dizocilpine and certain sigma ligands and that some imidazoline compounds can also bind to this site. We have investigated whether interaction with this binding site could account for the ability of imidazolines to stimulate insulin secretion from rat islets. Neither PCP nor dizocilpine shared the insulin secretory activity of the imidazoline efaroxan in rat islets suggesting that they do not have similar actions in the pancreatic B-cell. Further, we were able to define a new antagonist, KU14R (2(2-ethyl 2,3-dihydro-2-benzofuranyl)-2-imidazole), which selectively blocks the insulin secretory response to imidazolines. The results suggest that imidazolines do not stimulate insulin secretion by causing physical blockade of the K(+)-ATP channel in pancreatic B-cells and show that their effects are not reproduced by PCP or sigma receptor ligands.

Characterisation of new efaroxan derivatives for use in purification of imidazoline-binding sites.

The insulin secretagogue activity of certain imidazoline compounds is mediated by a binding site associated with ATP-sensitive K+ (K(ATP)) channels in the pancreatic beta-cell. We describe the effects of a series of structural modifications to efaroxan on its activity at this site. Substitution of amino-, nitro- or azide- groups onto the 5-position of the benzene ring of efaroxan did not significantly affect the functional interaction of the ligand with the islet imidazoline binding site. Modification of the imidazoline ring to an imidazole to generate 2-(2-ethyl-2,3-dihydrobenzo[b]furan-2-yl)-1H-imidazole (KU14R) resulted in loss of secretagogue activity. Indeed, this reagent appeared to act as an imidazoline antagonist since it blocked the secretory responses to imidazoline compounds and also inhibited the blockade of beta-cell K(ATP) channels by efaroxan in patch clamp experiments. Application of KU14R alone resulted in a modest reduction in K(ATP) channel opening, suggesting that it may display weak partial agonism, at least in patch-clamp experiments.

Clotrimazole and efaroxan stimulate insulin secretion by different mechanisms in rat pancreatic islets.

It is now well established that the imidazoline insulin secretagogue efaroxan mediates its effects by inducing closure of ATP-sensitive potassium channels in the pancreatic beta-cell, leading to membrane depolarisation, Ca2+ influx and increased insulin secretion. However, a recent study has shown that efaroxan may also act as a blocker of a second class of potassium channel (the Kmaxi channel) in red blood cells, raising the possibility that its effects in islets could be mediated by interactions with both types of channel. Since the antimycotic imidazole compound clotrimazole is a highly potent blocker of Kmaxi channels, we have studied the effects of this drug on insulin secretion. Clotrimazole stimulated insulin secretion from rat islets of Langerhans incubated in the presence of 6 mM glucose, in a dose-dependent manner. Experiments performed at different glucose concentrations showed that the actions of clotrimazole were most prominent at low glucose concentrations whereas it did not enhance secretion beyond the rate induced by 20 mM glucose. The insulinotropic action of clotrimazole was temperature dependent but was independent of extracellular calcium. Clotrimazole appeared to block ATP-sensitive potassium channels in islets since, like efaroxan and glibencamide, it was able to prevent the inhibitory effects of diazoxide on glucose-induced insulin secretion. However, neither the direct stimulatory effect of clotrimazole on insulin release nor the abilty of clotrimazole to reverse the inhibitory actions of diazoxide was sensitive to blockade by the imidazoline secretagogue antagonist KU14R. Overall, the results suggest that clotrimazole exerts an insulinotropic effect in pancreatic beta-cells that is distinct from the actions of imidazoline secretagogues such as efaroxan. Clotrimazole can increase insulin secretion at sub-maximal glucose concentrations by an action which appears to be independent of membrane ion channel events.

Group G streptococcal endocarditis: two case reports, a review of the literature and recommendations for treatment.

Two cases of endocarditis caused by a group G streptococcus are reported and the literature on group G streptococcal endocarditis is reviewed. The onset of illness is usually acute and the portal of entry for the organism through the skin. The left side of the heart is mainly involved and in about 50% cases the endocarditis arises on a normal valve. Most patients develop complications, both embolic and cardiac, and the mortality is high (36%). We suggest that patients with proven group G streptococcal endocarditis should be treated with large doses of benzyl penicillin and with an aminoglycoside for not less than 4 weeks. Patients with complications should be referred to a cardiothoracic centre. We should be glad to know details of complications, treatment and outcome in other cases of group G streptococcal endocarditis.

Vancomycin.

Vancomycin is an important antibiotic for the treatment of severe Gram-positive infection, especially in cases with resistant organisms or when the patient is allergic to penicillin. Because of its mode of action, pharmacokinetics and side effects, close liaison with the medical microbiologist is necessary.

Clinicians' guide to antibiotics. Tetracycline.

Tetracyclines have a broad range of activity against many organisms and remain the antibiotics of choice for some diseases, including brucellosis, chlamydial infections and severe acne vulgaris. However, because of their side effects, increasing resistance and the alternative antibiotics now available, their clinical usefulness is limited.