Incidence, clinical spectrum, diagnostic features, treatment and predictors of paradoxical reactions during antibiotic treatment of Mycobacterium ulcerans infections

Background: Paradoxical reactions from antibiotic treatment of Mycobacterium ulcerans have recently been recognized. Data is lacking regarding their incidence, clinical and diagnostic features, treatment, outcomes and risk factors in an Australian population.

Methods: Data was collected prospectively on all confirmed cases of M. ulcerans infection managed at Barwon Health Services, Australia, from 1/1/1998-31/12/2011. Paradoxical reactions were defined on clinical and histological criteria and cases were determined by retrospectively reviewing the clinical history and histology of excised lesions. A Poisson regression model was used to examine associations with paradoxical reactions.

Results: Thirty-two of 156 (21%) patients developed paradoxical reactions a median 39 days (IQR 20-73 days) from antibiotic initiation. Forty-two paradoxical episodes occurred with 26 (81%) patients experiencing one and 6 (19%) multiple episodes. Thirty-two (76%) episodes occurred during antibiotic treatment and 10 (24%) episodes occurred a median 37 days after antibiotic treatment. The reaction site involved the original lesion (wound) in 23 (55%), was separate to but within 3 cm of the original lesion (local) in 11 (26%) and was more than 3 cm from the original lesion (distant) in 8 (19%) episodes. Mycobacterial cultures were negative in 33/33 (100%) paradoxical episodes. Post-February 2009 treatment involved more cases with no antibiotic modifications (12/15 compared with 11/27, OR 5.82, 95% CI 1.12-34.07, p = 0.02) and no further surgery (9/15 compared with 2/27, OR 18.75, 95% CI 2.62-172.73, p < 0.001). Six severe cases received prednisone with marked clinical improvement. On multivariable analysis, age ≥ 60 years (RR 2.84, 95% CI 1.12-7.17, p = 0.03), an oedematous lesion (RR 3.44, 95% CI 1.11-10.70, p=0.03) and use of amikacin in the initial antibiotic regimen (RR 6.33, 95% CI 2.09-19.18, p < 0.01) were associated with an increased incidence of paradoxical reactions.

Conclusions: Paradoxical reactions occur frequently during or after antibiotic treatment of M. ulcerans infections in an Australian population and may be increased in older adults, oedematous disease forms, and in those treated with amikacin. Recognition of paradoxical reactions led to changes in management with less surgery, fewer antibiotic modifications and use of prednisolone for severe reactions.

Mycobacterium ulcerans treatment - can antibiotic duration be reduced in selected patients?

Mycobacterium ulcerans (M. ulcerans) is a necrotizing skin infection endemic to the Bellarine Peninsula, Australia. Current treatment recommendations include 8 weeks of combination antibiotics, with adjuvant surgery if necessary. However, antibiotic toxicity often results in early treatment cessation and local experience suggests that shorter antibiotic courses may be effective with concurrent surgery. We report the outcomes of patients in the Barwon Health M. ulcerans cohort who received shorter courses of antibiotic therapy than 8 weeks. A retrospective analysis was performed of all M. ulcerans infections treated at Barwon Health from March 1, 1998 to July 31, 2013. Sixty-two patients, with a median age of 65 years, received < 56 days of antibiotics and 51 (82%) of these patients underwent concurrent surgical excision. Most received a two-drug regimen of rifampicin combined with either ciprofloxacin or clarithromycin for a median 29 days (IQR 21–41days). Cessation rates were 55% for adverse events and 36% based on clinician decision. The overall success rate was 95% (98% with concurrent surgery; 82% with antibiotics alone) with a 50% success rate for those who received < 14 days of antibiotics increasing to 94% if they received 14–27 days and 100% for 28–55 days (p<0.01). A 100% success rate was seen for concurrent surgery and 14–27 days of antibiotics versus 67% for concurrent surgery and < 14 days of antibiotics (p = 0.12). No previously identified risk factors for treatment failure with surgery alone were associated with reduced treatment success rates with < 56 days of antibiotics. In selected patients, antibiotic treatment durations for M. ulcerans shorter than the current WHO recommended 8 weeks duration may be associated with successful outcomes.

Treatment and prevention of Mycobacterium ulcerans infection (Buruli ulcer) in Australia: guideline update

• Guidelines reflecting contemporary clinical practice in the management of Buruli ulcer (Mycobacterium ulcerans infection) in Australia were published in 2007.

• Management has continued to evolve, as new evidence has become available from randomised trials, case series and increasing clinical experience with oral antibiotic therapy.

• Therefore, guidelines on the diagnosis, treatment and prevention of Buruli ulcer in Australia have been updated. They include guidance on the new role of antibiotics as first-line therapy; the shortened duration of antibiotic treatment and the use of all-oral antibiotic regimens; the continued importance, timing and role of surgery; the recognition and management of paradoxical reactions during antibiotic treatment; and updates on the prevention of disease.

Ischaemic heart disease and Australian immigrants: the influence of birthplace and language skills on treatment and use of health services

Admission rates for ischaemic heart disease (IHD), and the use of invasive cardiovascular procedures, separation mode and length of stay (LOS) were compared between Australians from non-English speaking background (NESB; n=8627) and English speaking background (ESB; n=13162) aged 20 years and over admitted to Victorian urban public hospitals. The study covered the period from 1993 to 1998. It was found that, compared with their ESB counterparts, the incidence of admission for acute myocardial infarction was significantly higher for NESB men and women before and after controlling for confounding factors. The age-adjusted ratios for NESB women compared with their ESB counterparts ranged from 1.23 to 1.89 for cardiac catheterisation, from 0.23 to 0.27 for percutaneous transluminal coronary angioplasty (PTCA), and from 1.04 to 1.80 for coronary artery bypass grafting (CABG).
Procedure rates were comparable in men for cardiac catheterisation and CABG but higher for PTA rates in NESB men (OR: 1.29, 95%CI: 1.11-1.50) than their ESB counterparts. Both NESB men (β=0.04, 95%CI: 0.01-0.07) and women (β=0.03, 95%CI: 0.02-0.08) experienced significantly longer hospital stays than their ESB counterparts. These findings indicate there may be systematic differences in patients’ treatment and service utilisation in Victorian public hospitals. The extent to which physicians’ bias and
patients’ choice could explain these differences requires further investigation.

Prevalence, awareness, treatment, and control of hypertension in China data from the China National Nutrition and Health Survey 2002

Background— The present article aims to provide accurate estimates of the prevalence, awareness, treatment, and control of hypertension in adults in China.

Methods and Results— Data were obtained from sphygmomanometer measurements and an administered questionnaire from 141 892 Chinese adults 18 years of age who participated in the 2002 China National Nutrition and Health Survey. In 2002, 153 million Chinese adults were hypertensive. The prevalence was higher among men than women (20% versus 17%; P<0.001) and was higher in successive age groups. Overall, the prevalence of hypertension was higher in urban compared with rural areas in men (23% versus 18%; P<0.01) and women (18% versus 16%; P<0.001). Of the 24% affected individuals who were aware of their condition, 78% were treated and 19% were adequately controlled. Despite evidence to suggest improved levels of treatment in individuals with hypertension over the past decade, compared with estimates from 1991, the ratio of controlled to treated hypertension has remained largely unchanged at 1:4.

Conclusions— One in 6 Chinese adults is hypertensive, but only one quarter are aware of their condition. Despite increased rates of blood pressure–lowering treatment, few have their hypertension effectively controlled. National hypertension programs must focus on improving awareness in the wider community, as well as treatment and control, to prevent many tens of thousands of cardiovascular-related deaths.

Manualised treatment and dropout : a study of parent training

Parents who dropped out of manualised parent training programs for children with externalising behaviour disorders were interviewed retrospectively and compared prospectively with parents who continued in these programs. Parents who dropped out tended to feel more overwhelmed by their situation, because their child's behaviour problems were more severe, they had single parent status or had more than one child with difficulties.

An investigation into the ion-exchange properties of chemically modified wool for use in water treatment and chromatography

This study was undertaken to investigate the suitability of natural and chemically treated wool fibres for use in water treatment and in the separation of constituents for monitoring contaminants in water.

Experimental work was carried out to determine the ability of natural and treated wool fibres to remove these constituents from water,

This study provided information on the characteristics of the wool fibre as a medium in water treatment.

Does cigarette promotion increase susceptibility to smoking? : a re-test of the link between tobacco industry promotion and adolescent susceptibility to cigarette use

In 1998, using the Index of Receptivity to Tobacco Industry Promotion (IRTIP), it was claimed that tobacco promotion increased youth susceptibility to smoking. Arguably, this claim started the belief that ?cigarette advertising causes smoking? and led to many countries severely restricting cigarette promotion. The problem is, ten years lat... more »er, youth are still lighting up. Could they have gotten it wrong? The IRTIP procedure is widely used to model the link between promotional activities and susceptibility to product use. It is now being used for other products like alcohol, fast-food and colas. This book reports the results of a verification and re-test of the IRTIP model. Using the original data, it was found that IRTIP magnifies Response-Style and Respondent Drop-Out Biases. These biases are shown to lead to the finding of a positive link between tobacco promotion and susceptibility to smoking. Because the IRTIP process is biased, it may be prudent to revisit the many research studies that have used this procedure. The faulty 1998 claim may have harmed efforts to control and limit the use of cigarettes.

Re-testing the link between youth receptivity to tobacco promotion and their susceptibility to smoke

The Index of Receptivity to Tobacco Industry Promotion (IRTIP) is a model that is used by hundreds of articles. The causal claim based on findings from this model is even more pervasive, and has resulted in much of the modern post 1998 tobacco legislation that is still enforced. This thesis tested the link between adolescent receptivity to tobacco industry promotion and susceptibility to smoking. Pierce et al. (1998) reported that they had found a positive and causal association between receptivity and susceptibility by using IRTIP. They claimed that receptivity to tobacco industry promotion was the only significant causal factor affecting adolescent susceptibility to smoking. Exposure to peer and parental smoking was not found to be a significant effect. A review of the literature found that many sections of IRTIP differ from accepted marketing theory on how cigarette advertising and promotions affect adolescent adoption of cigarette smoking. The proxy measures used in IRTIP were shown to diverge from those previously used for measuring the constructs of Attention, Intention, Desire and Action (AIDA) in marketing communications. IRTIP also differs from previous theory by including measures that attempt to quantify the effect of tobacco premiums into a model that was designed to measure the effects of advertising.