A change in the NICE guidelines on antibiotic prophylaxis.

Since 2008, NICE clinical guidelines have stated: 'Antibiotic prophylaxis against infective endocarditis is not recommended for people undergoing dental procedures'. This put UK guidance at odds with guidance in the rest of the world, where antibiotic prophylaxis is recommended for patients at high-risk of infective endocarditis undergoing invasive dental procedures. Many dentists also felt this wording prohibited the use of antibiotic prophylaxis, regardless of the wishes of the patient or their personal risk of infective endocarditis and made it difficult for them to use their clinical judgment to deliver individualised care in the best interests of their patients. NICE have now changed this guidance to 'Antibiotic prophylaxis against infective endocarditis is not recommended routinely for people undergoing dental procedures.' This article examines the implications of this small but important change.

Guidelines on prophylaxis to prevent infective endocarditis.

Infective endocarditis is a devastating disease with high morbidity and mortality. The link to oral bacteria has been known for many decades and has caused ongoing concern for dentists, patients and cardiologists. Since 2008, the UK has been out of step with the rest of the world where antibiotic prophylaxis is recommended for high-risk patients undergoing invasive dental procedures. Recent evidence that identified an increase in endocarditis incidence prompted a guideline review by NICE and the European Society for Cardiology--which produces guidance for the whole of Europe. Despite reviewing the same evidence they reached completely opposing conclusions. The resulting conflict of opinions and guidance is confusing and poses difficulties for dentists, cardiologists and their patients. Recent changes in the law on consent, however, may provide a patient-centred and pragmatic solution to these problems. This Opinion piece examines the evidence and opposing guidance on antibiotic prophylaxis in the context of the recent changes in the law on consent and provides a framework for how patients at risk of endocarditis might be managed in practice.

NICE and antibiotic prophylaxis to prevent endocarditis.

Infective endocarditis is a devastating disease with high morbidity and mortality. The link to oral bacteria has been known for many decades and has caused on going concern for dentists, patients and cardiologists. Good oral hygiene has long been advocated to prevent endocarditis. Before 2008, antibiotic prophylaxis before invasive dental procedures was also an important strategy for preventing infective endocarditis for patients at risk of the disease in the UK, and still is in most other countries of the world. In 2008, however, NICE published new guidance recommending that antibiotic prophylaxis in the UK should cease. At the time this was a highly controversial decision. New data suggests that there has been a significant increase in the incidence of infective endocarditis since the 2008 guidelines. The 2008 guidance is being reviewed and draft new guidance is being put out for public consultation. This article discusses the issues raised by the new data and the questions that should be addressed in the review and public consultation.

Susceptibility of Cryptococcus neoformans by the NCCLS microdilution and Etest methods using five defined media.

The susceptibility of 12 isolates of Cryptococcus neoformans to amphotericin B, 5-fluorocytosine, fluconazole, itraconazole and ketoconazole was tested using the NCCLS and Etest methods with yeast nitrogen base (YNB) pH 5.6 and pH 7.0, RPMI MOPS pH 7.0 with and without added glucose (2%) and RPMI buffered with phosphate buffer to pH 7.0. Some isolates yielded poor growth in RPMI MOPS after 72 h. Tests indicated that YNB pH 5.6 was the best medium for 5-fluorocytosine but was unsuitable for ketoconazole. In conclusion, YNB pH 7.0 or RPMI MOPS with 2% glucose can be used with either method.

An outbreak of methicillin-resistant staphylococcus aureus (MRSA) in a dermatology day-care unit.

We describe an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in a dermatology day-care unit and the methods used to determine the mechanism of spread and control it. The epidemic strain had a characteristic sensitivity pattern and was typeable with phages 29, 80, 95, 47, 54 and 77, which was of considerable value in interpreting the epidemiological data. The method of spread was studied by examination of the medical and nursing records of patients who had acquired MRSA (to determine which members of staff they had encountered and which other MRSA-positive patients had been present in the department at the same time) and by the microbiological screening of all patients and staff. However, screening of all staff by nasal swabbing failed to identify carriage of the epidemic strain, while extensive swabbing of surfaces on the day-care unit also failed to show any evidence of MRSA in the environment. This suggests that the MRSA was most probably spread from patient to patient via the hands of staff, although there was also the possibility of direct transmission from patient to patient. Nine patients acquired the unique strain of MRSA and once acquired it proved difficult to eradicate, although in the majority, the infection did not appear to be clinically significant. However, in two patients MRSA contributed to a fatal outcome: these were the two most elderly patients and were the only two who were receiving systemic corticosteroids. The outbreak was brought under control with rigorous hygienic measures and the decision to discharge all patients with MRSA from the day-care unit. Repeat screening (swabs of nose, axilla and groin) of all day-care unit and in-patients 11 months after the last MRSA case showed no evidence of any residual MRSA infection in the day-care unit.

Unresponsive HIV-related oro-oesophageal candidosis--an evaluation of two new in-vitro azole susceptibility tests.

Azole-resistant HIV-related candidosis is increasingly recognized. We evaluated two new in-vitro susceptibility tests (the NCCLS proposed MIC method and Odds' assessment of relative growth in single anti-fungal concentration) as predictors of the clinical outcome of 66 HIV-positive patients with oral candidosis, of whom 22 were azole naive, 27 had always previously responded to azole therapy and 17 had persistent candidosis unresponsive to 7 days of standard azole therapy. None of the last group responded to increased daily doses of fluconazole or itraconazole capsules, though nine responded to itraconazole cyclodextrin solution 200 mg bd for 7 days. Our findings suggest that agreement between the Odds' test and the MIC method was excellent (96-98%) and that both could discriminate between isolates of azole-unresponsive patients and those of azole-responsive patients. For fluconazole susceptibility an MIC > or = 8 mg/L detected fluconazole-unresponsive patients with a sensitivity of 94% and specificity of 100%; Odds' method achieved 100% sensitivity and 100% specificity using all cut-offs between 77 and 88% relative growth in medium containing fluconazole (10(-5) M; 3 mg/L). For itraconazole and ketoconazole agreement between MIC and Odds' method was again excellent (98% and 96%, respectively) but five azole-unresponsive patients appeared to have ketoconazole-susceptible organisms as defined by both tests, and similarly 11 appeared to have itraconazole-susceptible organisms by both tests despite failing to respond to the capsule formulation of the drug. Of these 11, eight responded to itraconazole solution; this finding implies that itraconazole capsule failure might represent poor drug absorption rather than fungal resistance.

Comparison of a new insertion element, IS1407, with established molecular markers for the characterization of Mycobacterium celatum.

Genomic analyses of 18 Mycobacterium celatum strains obtained from different patients in three countries (United States, United Kingdom, and France) were performed; the methods used in this study were restriction fragment length polymorphism (RFLP) analysis, pulsed-field gel electrophoresis (PFGE) analysis, and PCR restriction analysis (PRA) of the hsp-65 gene. A new insertion sequence, IS1407 (GenBank accession no. X97307), belonging to the IS256 family, was identified in M. celatum type 1 strains and was characterized by sequencing. When a probe for Mycobacterium xenopi IS1395-like sequences was used, the RFLP analysis of M. celatum type 1 strains revealed that they contained three or four copies of IS1407 in identical genomic positions, while this element was absent in all M. celatum type 2 strains. PFGE performed with three different endonucleases revealed a unique large restriction fragment (LRF) pattern for M. celatum type 1 strains, whereas the LRF patterns obtained for M. celatum type 2 strains were polymorphic. Moreover, PFGE of nondigested genomic DNA revealed extrachromosomal elements in M. celatum type 2. The type strain of M. celatum type 3 could not be differentiated from M. celatum type 1 strains on the basis of the results of the RFLP analysis, the PFGE analysis, and the PRA of IS1407. In this study we confirmed that M. celatum types 1 and 2 represent distinct genomic clusters and that the molecular markers in M. celatum type 2 exhibit greater polymorphism than the molecular markers in M. celatum type 1.

Pilot studies of azithromycin, letrazuril and paromomycin in the treatment of cryptosporidiosis.

Pilot studies of the safety and efficacy of 3 drugs thought to have anticryptosporidial activity were carried out to determine whether any of them are suitable for large-scale clinical trials. Open studies of the use of azithromycin, letrazuril and paromomycin in patients with acquired immunodeficiency syndrome (AIDS) and confirmed cryptosporidial diarrhoea for at least a month. Azithromycin 500 mg daily was ineffective. Letrazuril 150-200 mg daily was associated with an improvement in symptoms in 40% of patients treated and cessation of excretion of cryptosporidial oocysts in the stool in 70%; however biopsies remained positive. Paromomycin therapy was associated with a complete resolution of diarrhoea in 60% of patients treated and some improvement in symptoms in a further 5% but it did not eliminate the infection. None of the drugs had any major toxicities. Dose escalation studies of azithromycin should be performed. Letrazuril should be further investigated for efficacy in double-blind placebo-controlled trials. Paromomycin appears to result in prolonged symptomatic remission of cryptosporidial diarrhoea, but has no effect on cryptosporidial cholangitis.

A new group (type 3) of Mycobacterium celatum isolated from AIDS patients in the London area.

We describe a new group (type 3) of the recently proposed species Mycobacterium celatum isolated from eight patients with AIDS in London, England. Sequences of genes coding for 16S rRNA (EMBL accession no. Z46664) showed a divergence of 17 bases from M. celatum type 2 reference isolates and a divergence of 7 bases from M. celatum type 1 reference isolates. A reference strain is available (NCTC 12882).

Rapid identification of mycobacteria from AIDS patients by capillary electrophoretic profiling of amplified SOD gene.

Aim-Rapid differentiation of mycobacterial species at the genomic level.Methods-The manganese superoxide dismutase (SOD) gene (464 bp) and 16SrRNA (353 bp) from 104 isolates (18 species) of mycobacteria were amplified using polymerase chain reaction (PCR). Products were sequenced and a phenogram of SOD sequences derived. PCR products of SOD gene were digested with HaeIII, and restriction fragment profiles visualised using capillary electrophoresis.Results-Novel SOD sequences were found for M szulgai, M marinum, M phlei, M smegmatis, M chelonei, M paratuberculosis, M malmoense, M intracellulare serotype 7, M intracellulare serotype 18, and M celatum types 1, 2, and 3. Phylogenetic analysis indicated that 18 of 19 species studied had 8-29% interspecies and <6% intraspecies sequence diversity in the SOD gene. No consistent differences were detected between AIDS and non-AIDS isolates. M paratuberculosis showed a unique SOD sequence with a 1.1% (SD 0.5%) diversity from M avium. Capillary electrophoresis profiles were able to differentiate 16 of 18 species within 24 hours.Conclusions-A phenogram of SOD sequences clearly delineated all mycobacterial species and showed two distinct clusters, fast growing species, and the M avium complex (MAC). Within the MAC, M avium (five types), M intracellulare (five types), M scrofulaceum (two types), and M paratuberculosis (one type) could be demonstrated. Phylogenetic diversity of M celatum from MAC, previously suggested by 16SrRNA data, was confirmed. This simple and rapid method for DNA extraction, in conjunction with capillary electrophoresis of SOD restriction fragments, allows rapid identification of mycobacterial isolates.

False negative results in enzyme linked immunosorbent assays using synthetic HIV antigens.

The sensitivity of 12 commonly used anti-HIV-1/HIV-2 enzyme immunoassays was evaluated. The assays, each of which utilises at least one synthetic HIV antigen, were tested against a panel of 1092 specimens previously designated anti-HIV positive. In a total of 13 104 tests there were eight false negative results attributable to assay insensitivity: three were on two serum samples collected close to seroconverison and five on another serum specimen. These eight false negative results arose in seven different assays. Five other false results were attributable to technical error. This false negativity rate indicates that all of the assays performed adequately and leads to an estimate of one false negative result in a thousand tests in routine diagnostic practice. Because of the antigenic heterogeneity of HIV strains, similar evaluations would be required in several regions before this satisfactory level of sensitivity in anti-HIV assays incorporating synthetic antigens could be said to be universal.