Hiten Thaker

Low prevalence of transmitted antiretroviral drug resistance in a large UK HIV-1 cohort

OBJECTIVES To describe current practice in testing for transmitted antiretroviral drug resistance (TDR) and the prevalence of TDR in a large UK HIV-1 cohort. METHODS The study includes a retrospective analysis of newly diagnosed HIV-1-infected patients presenting to eight HIV clinics in the north of England between March 2005 and March 2007. Resistance mutations were defined by IAS-USA. Predicted phenotypes were calculated by the Stanford University database. RESULTS Five hundred and fifty-eight patients were studied, of whom 394 (70.6%) had heterosexually acquired HIV and 377 (67.6%) were infected outside the UK. TDR testing was performed in 406 patients (72.8%). Thirteen of 392 viral resistance profiles (3.3%) showed genotypic TDR. There was no significant association between TDR and any demographic or risk factor or baseline CD4 count. In particular, rates of TDR were similar in white British (6/147, 4.1%) and black African (7/224, 3.1%) patients. The numbers of patients with TDR to individual drug classes were: nucleoside reverse transcriptase inhibitors, 2 (0.5%); non-nucleoside reverse transcriptase inhibitors, 7 (1.8%); and protease inhibitors, 4 (1.0%). No patients had multi-class resistance detected. Eleven patients (2.8%) were predicted to have significant phenotypic resistance to at least one drug. CONCLUSIONS In a large unselected UK cohort, with high coverage of TDR testing, the prevalence of TDR was low and is in accordance with recent data, showing a decrease in the prevalence of TDR in the UK. Differences in population mix did not appear to explain this low rate.

Long-term mortality following bloodstream infection

Bloodstream infection is associated with significant short-term mortality, but less is known about long-term outcome. We describe factors affecting mortality up to 3 years after bloodstream infection in a cohort of patients reviewed at the bedside by an infection specialist. Patients seen by the bacteraemia service of our infectious diseases department between June 2005 and November 2008 were included in analyses. Routine clinical data collected at the time of consultation, together with laboratory, demographic and outcome data were analysed to identify factors predicting death at 30 days and 3 years after bloodstream infection. Cox regression models for both time-points were constructed, together with Kaplan-Meier survival curves. In all, 322 bloodstream infections were recorded in 304 patients. The 30-day mortality was 15%, with a 3-year mortality of 49%. At 30 days after bacteraemia, in the Cox regression model, increasing age (p 0.003) and lower serum albumin (p 0.014) were predictive of death. At 3 years, age (p <0.0001) and albumin (p 0.004) remained significant predictors of death, with the presence of vascular disease (p 0.05) also significantly associated with mortality. If temperature was treated as a continuous variable then urea was significant (p 0.044); however, if temperature was categorized into hypothermia and non-hypothermia, then the presence of hypothermia (p 0.008) and chronic renal disease (p 0.034) became significant. There is an appreciable and gradual increase in mortality after an episode of bloodstream infection. Although many factors may not be amenable to intervention, patients at high risk of long-term mortality might require further follow up and assessment for potentially modifiable factors.

Healthcare associated discitis in the era of antimicrobial resistance.

Discitis is a recognized and serious complication of healthcare. We describe the cases of 4 patients, who presented to our unit over a 1 year period. All had exposure to healthcare before the onset of discitis and developed complex infections. There were no additional risk factors for discitis in any of the cases. The risk factors for discitis were peripheral intravenous cannulation in 1 case, intraabdominal surgery in 2 cases and multiple risks including intensive care admission and urethral catheterization in another case. The described cases demonstrate the importance of ascertaining a definitive microbiological diagnosis in healthcare associated discitis and the complex and expensive antibiotic regimens that may be required for the management of such cases. Clinicians should be aware when seeing patients with back pain and recent health care exposure that discitis can be present and complicated and that resistant organisms can be the cause.

Co-infection with human immunodeficiency virus and tuberculosis

The World Health Organisation (WHO) declared the global tuberculosis (TB) epidemic to be a public health emergency in 1993. Despite signs that the epidemic may be slowing down the actual number of TB cases continues to rise. HIV and TB are closely associated; HIV promotes the progression from latent TB infection to active disease and TB is the leading infectious killer of people living with HIV. Tuberculosis and HIV co-infection remains a complex disease where there are hurdles to cross at each state. Diagnosis and treatment are complex and involve a clear understanding of innovative laboratory methods as well as complex drug-drug interactions. This review article brings the reader up-to-date on the current thoughts on this co-infection and encourages more research in this area. (excerpt)

Penicillium marneffei presenting as an immune reconstitution inflammatory syndrome (IRIS) in a patient with advanced HIV

A 62-year-old British man with advanced HIV was established on antiretroviral therapy and treatment for disseminated Mycobacterium avium complex and Cytomegalovirus infections. One month later he re-presented with epigastric pain, an epigastric mass and skin lesions. Abdominal imaging revealed large volume lymphadenopathy, which was not present on previous imaging. Blood cultures yielded Penicillium marneffei, a dimorphic fungus endemic to South-east Asia. The patient had spent several years travelling in Thailand prior to the diagnosis of HIV. Penicilliosis is a common AIDS-defining illness in endemic areas, but remains rare in Europe. In this case, it presented in the context of a rapidly decreasing viral load as an immune reconstitution inflammatory syndrome. The challenges of management in the context of multiple comorbidities and polypharmacy are discussed.

Isoniazid-resistant intracranial tuberculoma treated with a combination of moxifloxacin and first-line anti-tuberculosis medication.

We report a case of a previously healthy 23-year-old Somalian care assistant. She presented with a 4 month history of persistent occipital headaches associated with intermittent nausea and vomiting. Computed tomography and magnetic resonance imaging of the brain showed a large enhancing lesion in the right cerebellar hemisphere with surrounding ring lesions, suggestive of an intracranial neoplasm with metastases. However, tuberculoma of the brain was confirmed based on histology of the excision biopsy and cerebrospinal fluid (CSF) culture results: Mycobacterium tuberculosis resistant to isoniazid (INH) with sensitivity to other standard drugs, including fluoroquinolones, was cultured from CSF. No primary focus to suggest spread from elsewhere was found. The patient was treated successfully with moxifloxacin, rifampicin, pyrazinamide and ethambutol. Isolated INH-resistant intracranial tuberculoma is rare in adults. It can mimic other intracranial masses and should be kept in mind, especially in populations with a high risk of tuberculosis. Clinical use of moxifloxacin in INH-resistant tuberculomas is limited in humans and this case demonstrates that moxifloxacin may be an effective alternative treatment.

An evaluation of the usefulness of Staphylococcus aureus serodiagnosis in clinical practice

The measurement of serum antibodies to Staphylococcus aureus has been used in the diagnosis of individuals with suspected deep-seated infection, particularly when culture is difficult or unproductive. The Health Protection Agency (HPA), UK, currently offers testing to detect antibodies to alpha haemolysin (staphylolysin) and the nuclease enzyme in parallel. However, a lack of high specificity and sensitivity of the anti-staphylolysin test has been demonstrated repeatedly in occult S. aureus infections [1–3], whilst there is little information on the usefulness of the anti-nuclease test. It is understood that serological tests, even in combination, are an imperfect marker of staphylococcal infection. It is unclear whether staphylococcal serological testing is useful in clinical practice. We undertook a retrospective evaluation of the use of staphylococcal serodiagnosis in the Hull and East Yorkshire NHS Trust. Our objectives were to determine the extent of testing, to identify the clinical context in which tests were requested, to ascertain whether the results contributed towards patient management and to inform the production of local guidelines. We retrospectively identified the results of serum antistaphylolysin and anti-nuclease titres collected from individuals presenting to a 1,500-bed teaching hospital over a 3-year period. Information concerning the demographics of the individual, their relevant hospital and/or outpatient attendances, past medical history, clinical diagnoses, microbiology, antimicrobial and medical management, and outcome was obtained from their clinical records and the trust pathology database. Test results were interpreted in accordance with HPA guidance [4]. A positive test was defined as an anti-staphylolysin titre of ≥8 units/ml and/or an anti-nuclease titre of >32 units/ml; an equivocal test (suggestive of staphylococcal infection), an antistaphylolysin titre of 4–6 units/ml and/or anti-nuclease titre of 32 units/ml; and a negative test (no evidence of staphylococcal infection or repeat testing required), an anti-staphylolysin titre of ≤2 units/ml and anti-nuclease titre of ≤16 units/ml. Serological testing was performed on 121 serum samples collected from 113 individuals between 1st September 2004 and 31st August 2007. Of these, 73 (65%) were male and their median age was 55 years (range 2–90). Testing was performed in both inpatient (81, 72%) and outpatient (32, 28%) hospital settings. Testing was requested on individuals managed by a variety of specialties, including infectious diseases (78, 70%), orthopaedics (11, 10%), cardiology (3, 2.7%), neurosurgery (3, 2.7%) and the acute medical admitting teams (16, 14.5%). Ninety (80%) individuals were managed as suspected or proven deep-seated infection, including cases of discitis, (20, 18%), prosthetic joint (15, 13%) and native (10, 9%) septic arthritis, osteomyelitis (18, 16%), soft tissue infection (15, 13%), infective endocarditis (10, 9%) and with bacteraemia of uncertain source (2, 1.7%). In the remainder (23, 20%), there was no evidence of infection. Test results were available a median of 14 days from the time of the serum sample collection. Repeat serology was performed on only six individuals. J. Elston (*) :M. Ling :B. Jeffs :K. Adams :H. Thaker : P. Moss :G. Barlow Department of Infection and Tropical Medicine, Main Administration block, Castle Hill Hospital, Cottingham, East Yorkshire HU16 5JQ, UK e-mail: jameselston2003@yahoo.co.uk

Severe myositis on commencement of efavirenz, abacavir and lamivudine, in the absence of lactic acidosis or classical abacavir hypersensitivity.

Myositis in HIV may be due to HIV itself, or to opportunistic infection, malignancy or drug treatment. Severe myositis or rhabdomyolysis have never been reported with the commonly used nucleoside reverse transcriptase inhibitor abacavir, although creatine phosphokinase may rise modestly, particularly if abacavir hypersensitivity occurs. We report an unusual case of abacavir use associated with a thousand-fold rise in creatine phosphokinase in the absence of features of hypersensitivity. The case was also notable firstly in that there was an absence of the HLA-B5701 allele, the most common human leucocyte antigen (HLA) allele associated with hypersensitivity, and, secondly, as the case occurred in an African patient, African people not being prone to abacavir hypersensitivity.

Oral voriconazole for invasive fungal skull base infection

BACKGROUND Intravenous amphotericin or intravenous voriconazole, both followed by oral voriconazole, have previously been given to treat invasive aspergillosis of the skull base. CASE REPORT Exclusively oral voriconazole was used in an immunocompetent patient with biopsy-proven, invasive aspergillosis. She had a large, erosive lesion extending from the central skull base to the right orbit and ethmoid sinus, and displacing the right internal carotid artery. After four months of oral treatment as an out-patient, a repeated computed tomography scan showed a fully treated infection with post-infectious changes only, and treatment was terminated. Two years later, there had been no recurrence. CONCLUSION Substantial cost savings were made by using exclusively oral treatment, compared with the use of intravenous voriconazole or amphotericin, or a switch strategy.

Study in pink...rash

An 18-year-old woman presented with a 1 day history of a rash that began centrally, over the abdomen, that progressed to cover the entirety of her body, most strikingly on her face. Five days prior to this presentation she suffered from fever, dry cough, abdominal pain, loose stools and myalgia. One week prior to admission she attended a convention hosted by the travelers community she belonged to; at this meeting she was exposed to three other young people with a similar history. …