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Biomedical subjects

Malcolm McDonald

Publications and source records attributed to Malcolm McDonald.

9 recordsLinked to original sources

Use of a single-nucleotide polymorphism genotyping system to demonstrate the unique epidemiology of methicillin-resistant Staphylococcus aureus in remote aboriginal communities.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a major public health problem in Australia, as in many other parts of the world. High rates of CA-MRSA skin and soft tissue infection have been reported from Aboriginal communities. We used a single-nucleotide polymorphism (SNP) genotyping typing system based on the multilocus sequence type (MLST) database to investigate the epidemiology of CA-MRSA and methicillin-sensitive S. aureus (MSSA) over a 12-month period in three remote Aboriginal communities of Northern Australia. This was supplemented by real-time PCR for Panton-Valentine leukocidin (PVL) genes, staphylococcal cassette chromosome mec (SCCmec) typing, and antimicrobial susceptibility testing. S. aureus was recovered from pyoderma lesions on 221 occasions and throat swabs on 44 occasions. The median monthly recovery rate of S. aureus from skin sores was 58% (interquartile range, 62 to 78%), and there was no seasonal variation. Twenty-three percent of isolates were CA-MRSA; the proportion was similar across the communities and did not vary over the study period. Erythromycin resistance was found in 47% of CA-MRSA and 21% of MSSA. SNP-based typing identified 14 different clonal complexes (cc); however, cc75 was predominant, accounting for 71% of CA-MRSA isolates. These were confirmed as ST75-like by using an additional SNP and MLST of selected isolates. All but one of the cc75 isolates had SSCmec type IV (one had type V), and all were PVL negative. Monthly tracking of SNP-based cc types showed a highly dynamic process. ST75-MRSA-IV appears to be unique to the region and probably evolved de novo in remote Aboriginal communities.

Australia↗

Recovering streptococci from the throat, a practical alternative to direct plating in remote tropical communities.

Throat swabs are regarded as the "gold standard" for diagnosing streptococcal pharyngitis and for surveillance research. Culturing throats in remote tropical settings is logistically difficult, and these settings are commonly burdened by high rates of streptococcal disease. The survival of streptococci on swabs may depend on whether they are of "throat" or "skin" type, as determined by emm pattern typing. The aims of this study were to compare the recovery rates of beta-hemolytic streptococci (BHS) using three different transport methods and to determine whether the recovery rates correlated with the emm pattern type. Monthly duplicate throat swabs were taken from occupants of selected households in three remote Aboriginal communities. Paired swabs were separated and handled in one of three ways: (i) direct inoculation onto culture media with cold-box transport (plated), (ii) sealed in a bag with a silica gel desiccant and cold-box transport (desiccant), and (iii) transport at ambient temperature and humidity (ambient). emm pattern typing was done by standard methods. Over 23 months, 4,842 throat swabs were taken, and 4,122 were paired. BHS were recovered on 11.5% of the 4,842 occasions (group A, 4.5%; group C, 1.7%; group G, 5.4%). Results from paired swabs showed the plated method was superior to desiccant and desiccant was better than ambient. Pooled data indicated that plated and desiccant were equivalent, and both were significantly better than ambient. There was no correlation between the emm pattern type and recovery of group A streptococci by different methods. In tropical and remote settings, cold-box transport with desiccant and subsequent inoculation of culture plates in the laboratory is a practical alternative to direct plating.

Bacteriological Techniques↗

The challenge of acute rheumatic fever diagnosis in a high-incidence population: a prospective study and proposed guidelines for diagnosis in Australia's Northern Territory.

BACKGROUND: Accurate diagnosis of acute rheumatic fever (ARF) remains problematic in high-incidence settings and especially in the Aboriginal population of Australia's Northern Territory. Previous investigators have demonstrated that strict application of the 1992 Updated Jones Criteria results in under-diagnosis. This study's objectives were to review use of the Jones Criteria (1992 Update) in diagnosing ARF in Australian Aboriginal patients presenting with suspected rheumatic fever, and formulate a locally relevant algorithm to improve diagnosis. METHODS: Patients presenting to Royal Darwin Hospital with suspected ARF were prospectively assessed during a 15-month period. Demographic information, clinical history, examination, laboratory and echocardiographic findings were documented in order to determine whether the Jones Criteria were fulfilled, and to identify alternative diagnoses. The hospital discharge diagnosis was recorded and patients were followed up 18-33 months later. RESULTS: Out of 35 patients with suspected ARF, all were Aboriginal Australians, 17 (49%) had a discharge diagnosis of definite ARF, 7 (20%) had definite non-rheumatic fever diagnoses (disseminated gonococcal infection, systemic lupus erythematosis, buttock abscess and other febrile illnesses in children with cardiac murmur due to previously undiagnosed RHD). The remaining 11 (31%) posed diagnostic difficulties because of mild symptoms that failed to fulfil Jones Criteria (attracting diagnoses such as 'unexplained arthralgia') or atypical features such as older age. Two patients whose illness initially failed to fulfil the Jones Criteria, who were neither diagnosed with ARF nor commenced on secondary benzathine penicillin prophylaxis, were found on follow-up to have definite and probable ARF, respectively. At least 29% (8/28) of patients without prior recognised ARF/RHD had echocardiographic evidence of established RHD, indicating that previous episodes were missed. CONCLUSIONS: Individual mild episodes of ARF may be overlooked, with patients missing out on the timely institution of secondary prophylaxis. The Jones Criteria should be supplemented by active exclusion of differential diagnoses and vigilant follow-up including echocardiography. 'Probable' and 'possible ARF' should be recognised as diagnostic categories applying to patients not fulfilling the Jones Criteria but who nevertheless should be offered prophylactic penicillin at least until further follow-up. A set of diagnostic guidelines is proposed.

Acute Disease↗

Assessment of a register-based rheumatic heart disease secondary prevention program in an Australian Aboriginal community.

OBJECTIVE: To assess specific performance indicators relating to a register-based acute rheumatic fever and rheumatic heart disease (ARF/RHD) prevention program in a remote Australian Aboriginal community in order to identify the most appropriate avenues for improvements in delivery of services. METHODS: Information kept on the central ARF/RHD register was compared with an amalgamated dataset from three other sources. The community clinic charts of identified patients were reviewed for information regarding accuracy of diagnosis and the number of doses of benzathine penicillin received in the last year. Specific follow-up arrangements were assessed and compared with practice guidelines. RESULTS: The central ARF/RHD register contained the names of 58 of the 72 (81%) people identified in the community as eligible for inclusion. Only 42% (22/52) of people receiving antibiotic prophylaxis had received 80% or more of the recommended doses in the previous year; service delivery was significantly better for females than males (p = 0.004). Individuals in priority category 1 (most severe disease) were found to be receiving follow-up and investigation according to guidelines. About half the people in categories 2 (moderate disease) and 3 (mild disease) had been inadequately investigated and/or missed out on follow-up appointments. CONCLUSIONS: The ARF/RHD prevention program in this large remote Aboriginal community is struggling to deliver services to a substantial proportion of people who require them. Specific interventions, especially those related to men's health, may be required to correct the problems.

Anti-Bacterial Agents↗

Acute rheumatic fever: a chink in the chain that links the heart to the throat?

Acute rheumatic fever (ARF) remains a major problem in tropical regions, resource-poor countries, and minority indigenous communities. It has long been thought that group A streptococcal (GAS) pharyngitis alone was responsible for acute rheumatic fever; this belief has been supported by laboratory and epidemiological evidence gathered over more than 60 years, mainly in temperate climates where GAS skin infection is uncommon. GAS strains have been characterised as either rheumatogenic or nephritogenic based on phenotypic and genotypic properties. Primary prevention strategies and vaccine development have long been based on these concepts. The epidemiology of ARF in Aboriginal communities of central and northern Australia challenges this view with reported rates of ARF and rheumatic heart disease (RHD) that are among the highest in the world. GAS throat colonisation is uncommon, however, and symptomatic GAS pharyngitis is rare; pyoderma is the major manifestation of GAS infection. Typical rheumatogenic strains do not occur. Moreover, group C and G streptococci have been shown to exchange key virulence determinants with GAS and are more commonly isolated from the throats of Aboriginal children. We suggest that GAS pyoderma and/or non-GAS infections are driving forces behind ARF in these communities and other high-incidence settings. The question needs to be resolved as a matter of urgency because current approaches to controlling ARF/RHD in Aboriginal communities have clearly been ineffective. New understanding of the pathogenesis of ARF would have an immediate effect on primary prevention strategies and vaccine development.

Acute Disease↗

Once-daily intravenous cefazolin plus oral probenecid is equivalent to once-daily intravenous ceftriaxone plus oral placebo for the treatment of moderate-to-severe cellulitis in adults.

A once-daily regimen of cefazolin (2 g intravenously [iv]) plus probenecid (1 g by mouth) was compared with a once-daily regimen of ceftriaxone (1 g iv) plus oral placebo in a randomized, double-blind equivalence trial of home-based therapy for moderate-to-severe cellulitis in adults. For the assessable recipients of cefazolin-probenecid (n=59) and ceftriaxone-placebo (n=57), clinical cure occurred at the end of treatment in 86% and 96% (P=.11), respectively, and was maintained at 1 month of follow-up in 96% and 91% (P=.55), respectively. The mean number of treatment doses (+/-standard deviation) given was similar in the 2 treatment arms (6.97+/-2.6 for cefazolin-probenecid and 6.12+/-2.1 for ceftriaxone-placebo; P=.06). The median antibiotic trough concentrations were 2.35 microgram/mL for cefazolin and 15.45 microgram/mL for ceftriaxone. Patients in the 2 treatment arms were similar with regard to overall rates of adverse reaction (P=.15), but nausea was more common among those in the cefazolin-probenecid arm (P=.048). The once-daily regimen of cefazolin-probenecid is a cheap, practical, and effective treatment option for moderate-to-severe cellulitis, and it avoids the need to use third-generation cephalosporins in most patients.

Administration, Oral↗

The changing profile of bacterial endocarditis as seen at an australian provincial centre.

BACKGROUND: The clinical profile of endocarditis has changed over the past four decades with studies showing trends towards increasing age, more nosocomial and prosthetic valve infection and increasing rates of Staphylococcus aureus infection. However, these studies have been biased by referral patterns. METHODS: We reviewed data collected at three hospitals in the Barwon-South-West region in Victoria, Australia. All cases identified between 1994 and 1999 were reviewed according to the Duke criteria. RESULTS: During this period, 58 patients were diagnosed as having endocarditis. The incidence rate during this time was 3.0 per 100 000 with a rise in the rate of admissions from 0.15 to 0.26 per 1000 from 1995 to 1999. Sixteen (28%) were nosocomial with the majority from line-related sepsis. No intravenous drug users were identified. Eighteen (31%) involved endovascular prosthetic material. S. aureus was the causative pathogen in 23 (40%), with 'viridans' streptococci contributing 12 (21%) and other organisms accounting for 12 (21%). Attributable mortality in this series was 17%. CONCLUSIONS: We have seen a rise in the rate of endocarditis during this time. The proportions of endocarditis due to S. aureus and 'viridans' streptococci, as well as rates of nosocomial and prosthetic valve infection, are consistent with more recent series at referral hospitals and district hospitals, representing a change since studies performed in the 1960s and 1970s. Our findings confirm a trend towards a clinical profile seen at referral centres and reinforce the emerging importance of S. aureus, nosocomial bacteraemia and prosthetic valve endocarditis.

Journal Article↗

Acute rheumatic fever.

Acute rheumatic fever (ARF) and its chronic sequela, rheumatic heart disease (RHD), have become rare in most affluent populations, but remain unchecked in developing countries and in some poor, mainly indigenous populations in wealthy countries. More than a century of research, mainly in North America and Europe, has improved our understanding of ARF and RHD. However, whether traditional views need to be updated in view of the epidemiological shift of the past 50 years is still to be established, and improved data from developing countries are needed. Doctors who work in populations with a high incidence of ARF are adapting existing diagnostic guidelines to increase their sensitivity. Group A streptococcal vaccines are still years away from being available and, even if the obstacles of serotype coverage and safety can be overcome, their cost could make them inaccessible to the populations that need them most. New approaches to primary prevention are needed given the limitations of primary prophylaxis as a population-based strategy. The most effective approach for control of ARF and RHD is secondary prophylaxis, which is best delivered as part of a coordinated control programme.

Acute Disease↗