A major pain in the hip - Destruction of the left acetabulum and femoral head secondary to Tuberculosis: A case report and review of the literature.

A 68-year-old-gentleman presented with left hip pain, night sweats, fatigue, and weight loss. He had previously experienced pain with white discharge until he underwent an arthroscopic washout and reduction. The left lower limb was shortened and wasted with limited hip movements. He had recently travelled to Zambia, his country of origin. Imaging demonstrated a large mass with chronic erosions of the acetabulum and femoral head. Synovial biopsy grew Mycobacterium tuberculosis, which was treated with rifampicin, isoniazid, pyrazinamide, and ethambutol for 2 months then 4 months of rifampicin and isoniazid. Whole genome sequencing indicated full sensitivity. Complex reconstructive surgery is scheduled, with a custom femoral head and acetabulum. This case illustrates the importance of considering tuberculosis in patients with erosive joint pathology and a multidisciplinary approach as delayed diagnosis results in high morbidity. Prompt diagnosis using newer modalities such as whole genome sequencing on synovial fluid can enable timely treatment.

Osmotic therapies added to antibiotics for acute bacterial meningitis.

BACKGROUND: Every day children and adults die from acute community-acquired bacterial meningitis, particularly in low-income countries, and survivors risk deafness, epilepsy and neurological disabilities. Osmotic therapies may attract extra-vascular fluid and reduce cerebral oedema, and thus reduce death and improve neurological outcomes.This is an update of a Cochrane Review first published in 2013. OBJECTIVES: To evaluate the effects of osmotic therapies added to antibiotics for acute bacterial meningitis in children and adults on mortality, deafness and neurological disability. SEARCH METHODS: We searched CENTRAL (2017, Issue 1), MEDLINE (1950 to 17 February 2017), Embase (1974 to 17 February 2017), CINAHL (1981 to 17 February 2017), LILACS (1982 to 17 February 2017) and registers of ongoing clinical trials (ClinicalTrials.com, WHO ICTRP) (21 February 2017). We also searched conference abstracts and contacted researchers in the field (up to 12 December 2015). SELECTION CRITERIA: Randomised controlled trials testing any osmotic therapy in adults or children with acute bacterial meningitis. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results and selected trials for inclusion. Results are presented using risk ratios (RR) and 95% confidence intervals (CI) and grouped according to whether the participants received steroids or not. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: We included five trials with 1451 participants. Four trials evaluated glycerol against placebo, and one evaluated glycerol against 50% dextrose; in addition three trials evaluated dexamethasone and one trial evaluated acetaminophen (paracetamol) in a factorial design. Stratified analysis shows no effect modification with steroids; we present aggregate effect estimates.Compared to placebo, glycerol probably has little or no effect on death in people with bacterial meningitis (RR 1.08, 95% CI 0.90 to 1.30; 5 studies, 1272 participants; moderate-certainty evidence), but may reduce neurological disability (RR 0.73, 95% CI 0.53 to 1.00; 5 studies, 1270 participants; low-certainty evidence).Glycerol may have little or no effect on seizures during treatment for meningitis (RR 1.08, 95% CI 0.90 to 1.30; 4 studies, 1090 participants; low-certainty evidence).Glycerol may reduce the risk of subsequent deafness (RR 0.64, 95% CI 0.44 to 0.93; 5 studies, 922 participants; low to moderate-certainty evidence).Glycerol probably has little or no effect on gastrointestinal bleeding (RR 0.93, 95% CI 0.39 to 2.19; 3 studies, 607 participants; moderate-certainty evidence). The evidence on nausea, vomiting and diarrhoea is uncertain (RR 1.09, 95% CI 0.81 to 1.47; 2 studies, 851 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: Glycerol was the only osmotic therapy evaluated, and data from trials to date have not demonstrated an effect on death. Glycerol may reduce neurological deficiency and deafness.

Retrospective analysis of the associations and effectiveness of performing therapeutic drug monitoring in pregnant HIV-positive women in two large centres in Manchester.

There is no proven benefit for the routine use of therapeutic drug monitoring in HIV-positive pregnant women either for improving viral control or preventing mother-to-child transmission. This analysis reviewed a cohort of 171 HIV-positive pregnant women delivering between 1 January 2008 and 28 May 2013 to first establish which baseline characteristics are associated with having therapeutic drug monitoring performed, and whether therapeutic drug monitoring was associated with improved HIV control during pregnancy or mother-to-child transmission. Therapeutic drug monitoring was performed in 39% ( n = 66) of patients; it was associated with baseline characteristics of poor adherence to therapy (therapeutic drug monitoring 23% versus non-therapeutic drug monitoring 10%, p = 0.025) and the use of protease inhibitors (therapeutic drug monitoring 94% versus non-therapeutic drug monitoring 77%, p = 0.005). By multivariate analysis therapeutic drug monitoring was associated with medication alterations during pregnancy (therapeutic drug monitoring 68% versus non-therapeutic drug monitoring 12%, p = < 0.001), but not associated with any difference in viral load breakthrough during pregnancy (therapeutic drug monitoring 12% versus non-therapeutic drug monitoring 7%, p = 0.456) and viral load detectable at birth (therapeutic drug monitoring 14% versus non-therapeutic drug monitoring 9%, p = 0.503). There were no instances of mother-to-child transmission. Therapeutic drug monitoring's association with medication changes is postulated as partially causal in this cohort. There was no evidence of any association with improved control or reduced transmission of HIV to advocate routine therapeutic drug monitoring use.

Prediction of Outcome From Adult Bacterial Meningitis in a High-HIV-Seroprevalence, Resource-Poor Setting Using the Malawi Adult Meningitis Score (MAMS).

Background: Acute bacterial meningitis (ABM) in adults residing in resource-poor countries is associated with mortality rates >50%. To improve outcome, interventional trials and standardized clinical algorithms are urgently required. To optimize these processes, we developed and validated an outcome prediction tool to identify ABM patients at greatest risk of death. Methods: We derived a nomogram using mortality predictors derived from a logistic regression model of a discovery database of adult Malawian patients with ABM (n = 523 [65%] cerebrospinal fluid [CSF] culture positive). We validated the nomogram internally using a bootstrap procedure and subsequently used the nomogram scores to further interpret the effects of adjunctive dexamethasone and glycerol using clinical trial data from Malawi. Results: ABM mortality at 6-week follow-up was 54%. Five of 15 variables tested were strongly associated with poor outcome (CSF culture positivity, CSF white blood cell count, hemoglobin, Glasgow Coma Scale, and pulse rate), and were used in the derivation of the Malawi Adult Meningitis Score (MAMS) nomogram. The C-index (area under the curve) was 0.76 (95% confidence interval, .71-.80) and calibration was good (Hosmer-Lemeshow C-statistic = 5.48, df = 8, P = .705). Harmful effects of adjunctive glycerol were observed in groups with relatively low predicted risk of poor outcome (25%-50% risk): Case Fatality Rate of 21% in the placebo group and 52% in the glycerol group (P < .001). This effect was not seen with adjunctive dexamethasone. Conclusions: MAMS provides a novel tool for predicting prognosis and improving interpretation of ABM clinical trials by risk stratification in resource-poor settings. Whether MAMS can be applied to non-HIV-endemic countries requires further evaluation.

The use of TDM in pregnant HIV-positive women: a retrospective cross-sectional review of five years practice in two large hospitals in Manchester.

INTRODUCTION: Despite plasma levels of certain HIV drugs decreasing in the third trimester of pregnancy there is no definitive evidence that therapeutic drug monitoring (TDM) improves HIV control and prevents mother-to-child transmission (MTCT). Indeed "one-off" TDM measurements are thought to poorly correlate with overall drug exposure [1]. We aim to describe baseline demographic and clinical characteristics of pregnant women with HIV, and to compare their HIV control, management during pregnancy and neonatal outcomes with respect to whether TDM was performed. MATERIALS AND METHODS: Retrospective cross-sectional case note analysis was performed on pregnant women with HIV who attended North Manchester General Hospital and Manchester Royal Infirmary from 1st January 2008 to 28th May 2013. RESULTS: A total of 171 pregnancies were included; 39% (n=66) had TDM. The majority of patients were of African origin (85%) and age range was 16-42 years (median 32 years). TDM was found to be associated with a history of poor adherence to therapy (TDM 23%, vs no TDM 10%, p=0.017), although baseline viral load (VL) and CD4 counts were comparable between TDM and non-TDM groups (p=0.4756 and 0.9492, respectively). TDM was also associated with protease inhibitors (PI) (TDM 94% vs no TDM 77%, p= 0.004). Within the PI group, TDM was more strongly associated with atazanavir use than other PI's (55%, p=0.023). TDM was not associated with any other demographic variable or with either of the two hospital sites (p=0.427). TDM was associated with medication alterations during pregnancy (TDM 67% vs no TDM 13%, p=0.052), but was not associated with any difference in outcomes with similar proportions of newly detectable VL during pregnancy (TDM 12% vs no TDM 7%, p=0.220) and VL detectable at birth (TDM 14% vs no TDM 9%, p= 0.293). There were no instances of MTCT. CONCLUSIONS: TDM was associated with PI use and a history of poor adherence at baseline. TDM was not associated with improved HIV control during pregnancy and there was no MTCT. TDM was not shown to have any additional benefit in pregnancy and its routine use is not recommended to improve HIV control or reduce MTCT.

Genomic pneumococcal load and CSF cytokines are not related to outcome in Malawian adults with meningitis.

OBJECTIVE: Bacterial meningitis in sub-Saharan Africa is predominantly caused by Streptococcus pneumoniae, is often associated with HIV co-infection and mortality rates are double those seen in better resourced settings. METHODS: To investigate the cause of this excessive mortality we quantified the pneumococcal DNA load and six common pro-inflammatory cytokines in the cerebrospinal fluid (CSF) of Malawian adults with culture proven pneumococcal meningitis and correlated the results to clinical parameters and outcome. There are currently no published data relating bacterial load to outcome in adults with pneumococcal meningitis. RESULTS: The mean age of patients was 32 years, 82% were HIV infected and 49% had died by day 40. CSF bacterial loads were high (median 6.5 × 10(5) copies/ml CSF) and there was no significant variation in bacterial load between survivors and non-survivors. All pro-inflammatory CSF cytokines were elevated in the CSF, with no clinically important differences between survivors and non-survivors. HIV status did not affect the CSF bacterial load or cytokine response. CONCLUSION: Mortality from pneumococcal meningitis in adults in sub-Saharan Africa is not related to pneumococcal bacterial load. More research is needed to understand the very high mortality from meningitis in this region.

High mortality amongst adolescents and adults with bacterial meningitis in sub-Saharan Africa: an analysis of 715 cases from Malawi.

UNLABELLED: Mortality from bacterial meningitis in African adults is significantly higher than those in better resourced settings and adjunctive therapeutic interventions such as dexamethasone and glycerol have been shown to be ineffective. We conducted a study analysing data from clinical trials of bacterial meningitis in Blantyre, Malawi to investigate the clinical parameters associated with this high mortality. METHODS: We searched for all clinical trials undertaken in Blantyre investigating bacterial meningitis from 1990 to the current time and combined the data from all included trial datasets into one database. We used logistic regression to relate individual clinical parameters to mortality. Adults with community acquired bacterial meningitis were included if the CSF culture isolate was consistent with meningitis or if the CSF white cell count was >100 cells/mm(3) (>50% neutrophils) in HIV negative participants and >5 cells/mm(3) in HIV positive participants. Outcome was measured by mortality at discharge from hospital (after 10 days of antibiotic therapy) and community follow up (day 40). RESULTS: Seven hundred and fifteen episodes of bacterial meningitis were evaluated. The mortality rate was 45% at day 10 and 54% at day 40. The most common pathogens were S.pneumoniae (84% of positive CSF isolates) and N.meningitidis (4%). 607/694 (87%) participants tested were HIV antibody positive. Treatment delays within the hospital system were marked. The median presenting GCS was 12/15, 17% had GCS<8 and 44.9% had a seizure during the illness. Coma, seizures, tachycardia and anaemia were all significantly associated with mortality on multivariate analysis. HIV status and pneumococcal culture positivity in the CSF were not associated with mortality. Adults with community acquired bacterial meningitis in Malawi present with a severe clinical phenotype. Predictors of high mortality are different to those seen in Western settings. Optimising in-hospital care and minimising treatment delays presents an opportunity to improve outcomes considerably.

Osmotic therapies added to antibiotics for acute bacterial meningitis.

BACKGROUND: Every day children and adults throughout the world die from acute community-acquired bacterial meningitis, particularly in low-income countries. Survivors are at risk of deafness, epilepsy and neurological disabilities. Osmotic therapies have been proposed as an adjunct to improve mortality and morbidity from bacterial meningitis. The theory is that they will attract extra-vascular fluid by osmosis and thus reduce cerebral oedema by moving excess water from the brain into the blood. The intention is to thus reduce death and improve neurological outcomes. OBJECTIVES: To evaluate the effects on mortality, deafness and neurological disability of osmotic therapies added to antibiotics for acute bacterial meningitis in children and adults. SEARCH METHODS: We searched CENTRAL 2012, Issue 11, MEDLINE (1950 to November week 3, 2012), EMBASE (1974 to November 2012), CINAHL (1981 to November 2012), LILACS (1982 to November 2012) and registers of ongoing clinical trials (April 2012). We also searched conference abstracts and contacted researchers in the field. SELECTION CRITERIA: Randomised controlled trials testing any osmotic therapy in adults or children with acute bacterial meningitis. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results and selected trials for inclusion. We collected data from each study for mortality, deafness, seizures and neurological disabilities. Results are presented using risk ratios (RR) and 95% confidence intervals (CI) and grouped according to whether the participants received steroids or not. MAIN RESULTS: Four trials were included comprising 1091 participants. All compared glycerol (a water-soluble sugar alcohol) with a control; in three trials this was a placebo, and in one a small amount of 50% dextrose. Three trials included comparators of dexamethasone alone or in combination with glycerol. As dexamethasone appeared to have no modifying effect, we aggregated results across arms where both treatment and control groups received corticosteroids and where both treatment and control groups did not.Compared to placebo, glycerol may have little or no effect on death in people with bacterial meningitis (RR 1.09, 95% confidence interval (CI) 0.89 to 1.33, 1091 participants, four trials, low-quality evidence); or on death and neurological disability combined (RR 1.04, 95% CI 0.86 to 1.25).Glycerol may have little or no effect on seizures during treatment for meningitis (RR 1.08, 95% CI 0.90 to 1.30, 909 participants, three trials, low-quality evidence).Glycerol may reduce the risk of subsequent deafness (RR 0.60, 95% CI 0.38 to 0.93, 741 participants, four trials, low-quality evidence). AUTHORS' CONCLUSIONS: The only osmotic diuretic to have undergone randomised evaluation is glycerol. Data from trials to date have not demonstrated benefit on death, but it may reduce deafness. Osmotic diuretics, including glycerol, should not be given to adults and children with bacterial meningitis unless as part of carefully conducted randomised controlled trial.

Strongyloides hyperinfection syndrome following resection of meningioma.

In this report, we present the case of a patient who developed the strongyloides hyperinfection syndrome 3 weeks after an uneventful resection of a sphenoid wing meningioma. She originally presented with symptoms of raised intracranial pressure and was given dexamethasone before surgery. The pathology, diagnosis and management of Strongyloides stercoralis are reviewed.

Epstein-barr virus coinfection in cerebrospinal fluid is associated with increased mortality in Malawian adults with bacterial meningitis.

Mortality from adult bacterial meningitis exceeds 50% in sub-Saharan Africa. We postulated that-particularly in individuals infected with human immunodeficiency virus (HIV)-herpes simplex virus, varicella zoster virus, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) in the cerebrospinal fluid (CSF) contribute to poor outcome. CSF from 149 Malawian adults with bacterial meningitis and 39 controls were analyzed using polymerase chain reaction. EBV was detected in 79 of 149 bacterial meningitis patients. Mortality (54%) was associated with higher CSF EBV load when adjusted for HIV (P = .01). CMV was detected in 11 of 115 HIV-infected patients, 8 of whom died. The mechanisms by which EBV and CMV contribute to poor outcome require further investigation.

Glycerol adjuvant therapy in adults with bacterial meningitis in a high HIV seroprevalence setting in Malawi: a double-blind, randomised controlled trial.

BACKGROUND: Southern Africa has a high incidence of bacterial meningitis in adults, often associated with HIV co-infection. Mortality exceeds 50%, even with appropriate antibiotic therapy, and is not improved with corticosteroids. Glycerol adjuvant therapy reduces long-term morbidity in bacterial meningitis in children, and its use is being promoted. We aimed to assess the effectiveness of glycerol as an adjuvant therapy for adults with bacterial meningitis in Africa. METHODS: The study was done in two phases. First, in an open-label dose-finding study, 45 adult patients with symptoms, signs, and cerebrospinal fluid findings consistent with bacterial meningitis received either 50 mL, 75 mL, or 100 mL of glycerol four times a day for 4 days. We then did a randomised, double-blind, placebo-controlled trial of oral glycerol in adults with bacterial meningitis. Patients with clinical and cerebrospinal fluid findings suggestive of bacterial meningitis were randomly assigned in blocks of 12 by use of a random number list produced by an independent statistician to receive either glycerol or an equivalent volume of sugar solution. Glycerol and placebo were indistinguishable by colour or taste. The primary outcome was mortality at 40 days, with secondary outcomes including disability and mortality restricted to pneumococcal disease. All patients were analysed for the primary outcome excluding those who were lost to follow-up. This trial is registered at controlled-trials.com, number ISRCTN70121840. FINDINGS: 75 mL glycerol four times a day was the highest tolerated dose, and was used for the main study. 265 patients were assigned treatment: 137 glycerol and 128 placebo. The trial was stopped early on the advice of the data and safety monitoring board after a planned interim analysis. By day 40, 61 (49%) of 125 patients in the placebo group and 86 (63%) of 136 in the glycerol group had died (adjusted odds ratio 2.4, 95% CI 1.3-4.2, p=0.003). There was no benefit from glycerol for death and disability by day 40, and glycerol did not improve death and disability by day 40 or death at day 40 in patients with proven bacterial disease or pneumococcal disease. Two serious adverse events occurred that were possibly due to the study drug. INTERPRETATION: Oral glycerol therapy cannot be recommended as an adjuvant therapy in adults with bacterial meningitis in resource-poor settings with a high HIV prevalence. FUNDING: Meningitis Research Foundation.

Cost-minimization analysis and audit of antibiotic management of bone and joint infections with ambulatory teicoplanin, in-patient care or outpatient oral linezolid therapy.

Bone and joint infections are significant causes of morbidity, mortality and healthcare costs. The cost of treatment for such infections is driven primarily by the length of hospital stay. Many of these infections will require treatment with prolonged periods of parenteral antibiotic therapy. Clinicians and healthcare managers are being attracted increasingly by administering treatment in the ambulatory setting as this offers clinical, economic and quality of life advantages from both the hospital's and patient's perspective. Our retrospective audit of managing 55 treatment episodes of bone and joint infections with teicoplanin delivered in the outpatient or home setting revealed that the mean cost of care per episode of infection was less with treatment in the ambulatory setting ( pound 1749.15) compared with the in-patient setting ( pound 11 400) or compared with the hypothetical situation of treatment with oral linezolid in the home setting ( pound 2546). Teicoplanin therapeutic drug monitoring appears to be valuable in establishing optimal serum levels, which appear to correlate with good clinical outcomes. The potential for alternative day or thrice weekly dosing with teicoplanin may offer further cost advantages whilst maintaining equivalent clinical effectiveness.